Stability Commitment
When available long term stability data on primary batches do not cover the proposed shelf life granted at the time of approval, a commitment should be made to continue the stability studies post approval in order to firmly establish the shelf life. Where the submission includes long term stability data from three production batches covering the proposed shelf life, a post approval commitment is considered unnecessary. Otherwise, one of the following commitments should be made:
1. If the submission includes data from stability studies on at least three production batches, a commitment should be made to continue the long term studies through the proposed shelf life and the accelerated studies for 6 months.
2. If the submission includes data from stability studies on fewer than three production batches, a commitment should be made to continue the long term studies through the proposed shelf life and the accelerated studies for 6 months, and to place additional production batches, to a total of at least three, on long term stability studies through the proposed shelf life and on accelerated studies for 6 months.
3. If the submission does not include stability data on production batches, a commitment should be made to place the first three production batches on long term stability studies through the proposed shelf life and on accelerated studies for 6 months. The stability protocol used for studies on commitment batches should be the same as that for the primary batches, unless otherwise scientifically justified. Where intermediate testing is called for by a significant change at the accelerated storage condition for the primary batches, testing on the commitment batches can be conducted at either the intermediate or the accelerated storage condition. However, if significant change occurs at the accelerated storage condition on the commitment batches, testing at the intermediate storage condition should also be conducted.
Evaluation
A systematic approach should be adopted in the presentation and evaluation of the stability information, which should include, as appropriate, results from the physical, chemical, biological, and microbiological tests, including particular attributes of the dosage form (for example, dissolution rate for solid oral dosage forms). The purpose of the stability study is to establish, based on testing a minimum of three batches of the drug product, a shelf life and label storage instructions applicable to all future batches of the drug product manufactured and packaged under similar circumstances. The degree of variability of individual batches affects the confidence that a future production batch will remain within specification throughout its shelf life. Where the data show so little degradation and so little variability that it is apparent from looking at the data that the requested shelf life will be granted, it is normally unnecessary to go through the formal statistical analysis; providing a justification for the omission should be sufficient.
An approach for analyzing data of a quantitative attribute that is expected to change with time is to determine the time at which the 95 one-sided confidence limit for the mean curve intersects the acceptance criterion. If analysis shows that the batch-to-batch variability is small, it is advantageous to combine the data into one overall estimate. This can be done by first applying appropriate statistical tests (e.g., p values for level of significance of rejection of more than 0.25) to the slopes of the regression lines and zero time intercepts for the individual batches. If it is inappropriate to combine data from several batches, the overall
shelf life should be based on the minimum time a batch can be expected to remain within acceptance criteria.
The nature of the degradation relationship will determine whether the data should be transformed for linear regression analysis. Usually the relationship can be represented by a linear, quadratic, or cubic function on an arithmetic or logarithmic scale. Statistical methods should be employed to test the goodness of fit on all batches and combined batches (where appropriate) to the assumed degradation line or curve.
Limited extrapolation of the real time data from the long term storage condition beyond the observed range to extend the shelf life can be undertaken at approval time, if justified. This justification should be based on what is known about the mechanisms of degradation, the results of testing under accelerated conditions, the goodness of fit of any mathematical model, batch size, existence of supporting stability data, etc. However, this extrapolation assumes that the same degradation relationship will continue to apply beyond the observed data.
Any evaluation should consider not only the assay but also the degradation products and other
appropriate attributes. Where appropriate, attention should be paid to reviewing the adequacy
of the mass balance and different stability and degradation performance.
Wednesday, March 30, 2011
Acetic Acid, Glacial
1 Nonproprietary Names
BP: Glacial Acetic Acid
JP: Glacial Acetic Acid
PhEur: Acetic Acid, Glacial
USP: Glacial Acetic Acid
2 Synonyms
Acidum aceticum glaciale; E260; ethanoic acid; ethylic acid;
methane carboxylic acid; vinegar acid.
3 Chemical Name and CAS Registry Number
Ethanolic acid [64-19-7]
4 Empirical Formula and Molecular Weight
C2H4O2 60.05
Functional Category
Acidifying agent.
Applications in Pharmaceutical Formulations or Technology Glacial and diluted acetic acid solutions are widely used as acidifying agents in a variety of pharmaceutical formulations and food preparations. Acetic acid is used in pharmaceutical products as a buffer system when combined with an acetate salt such as sodium acetate. Acetic acid is also claimed to have some antibacterial and antifungal properties.
Description
Glacial acetic acid occurs as a crystalline mass or a clear, colorless volatile solution with a pungent odor.Description Glacial acetic acid occurs as a crystalline mass or a clear, colorless volatile solution with a pungent odor.
Typical Properties
Acidity/alkalinity
pH = 2.4 (1M aqueous solution);
pH = 2.9 (0.1M aqueous solution);
pH = 3.4 (0.01M aqueous solution).
Boiling point is 1188C
Dissociation constant pKa = 4.76
Flash point 398C (closed cup); 578C (open cup).
Melting point 178C
Refractive index n D
20 = 1.3718
Solubility Miscible with ethanol, ether, glycerin, water, and other fixed and volatile oils.
Specific gravity is 1.045
Stability and Storage Conditions
Acetic acid should be stored in an airtight container in a cool, dry place.
Incompatibilities
Acetic acid reacts with alkaline substances.
Method of Manufacture
Acetic acid is usually made by one of three routes: acetaldehyde oxidation, involving direct air or oxygen oxidation of liquid acetaldehyde in the presence of manganese acetate, cobalt acetate, or copper acetate; liquid-phase oxidation of butane or naphtha; methanol carbonylation using a variety of techniques.
Safety
Acetic acid is widely used in pharmaceutical applications primarily to adjust the pH of formulations and is thus generally regarded as relatively nontoxic and nonirritant. However, glacial acetic acid or solutions containing over 50% w/w acetic acid in water or organic
solvents are considered corrosive and can cause damage to skin, eyes, nose, and mouth. If swallowed glacial acetic acid causes severe gastric irritation similar to that caused by hydrochloric acid.
(1) Dilute acetic acid solutions containing up to 10% w/w of acetic acid have been used topically following jellyfish stings.
(2) Dilute acetic acid solutions containing up to 5% w/w of acetic acid have also been applied topically to treat wounds and burns infected with Pseudomonas aeruginosa.
(3) The lowest lethal oral dose of glacial acetic acid in humans is reported to be 1470 mg/kg.
(4) The lowest lethal concentration on inhalation in humans is reported to be 816 ppm.Humans, are, however, estimated to consume approximately 1 g/day of acetic acid from the diet.
LD50 (mouse, IV): 0.525 g/kg(4)
LD50 (rabbit, skin): 1.06 g/kg
LD50 (rat, oral): 3.31 g/kg
Handling Precautions
Observe normal precautions appropriate to the circumstances and quantity of material handled. Acetic acid, particularly glacial acetic acid, can cause burns on contact with the skin, eyes, and mucous membranes. Splashes should be washed with copious quantities of water. Protective clothing, gloves, and eye protection are recommended.
Regulatory Status
GRAS listed. Accepted as a food additive in Europe. Included in the FDA Inactive Ingredients Database (injections, nasal, ophthalmic,and oral preparations). Included in parenteral and nonparenteral preparations licensed in the UK.
Related Substances
Acetic acid; artificial vinegar; dilute acetic acid.
Acetic acid
Comments: A diluted solution of glacial acetic acid containing 30–37% w/w of acetic acid.
Artificial vinegar
Comments: A solution containing 4% w/w of acetic acid.
Dilute acetic acid
Comments: A weak solution of acetic acid which may contain between 6–10% w/w of acetic acid.
In addition to glacial acetic acid, many pharmacopeias contain monographs for diluted acetic acid solutions of various strengths. For example, the USP32–NF27 has a monograph for acetic acid, which is defined as an acetic acid solution containing 36.0–37.0% w/w of acetic acid. Similarly, the BP 2009 contains separate monographs for glacial acetic acid, acetic acid (33%), and acetic acid (6%). Acetic acid (33%) BP 2009 contains 32.5–33.5% w/w of acetic acid. Acetic acid (6%) BP 2009 contains 5.7–6.3% w/w of acetic acid. The JP XV also contains a monograph for acetic acid that specifies that it contains 30.0–32.0% w/w of acetic acid. A specification for glacial acetic acid is contained in the Food Chemicals Codex (FCC). The EINECS number for acetic acid is 200-580-7. The PubChem Compound ID (CID) for glacial acetic acid is 176.
BP: Glacial Acetic Acid
JP: Glacial Acetic Acid
PhEur: Acetic Acid, Glacial
USP: Glacial Acetic Acid
2 Synonyms
Acidum aceticum glaciale; E260; ethanoic acid; ethylic acid;
methane carboxylic acid; vinegar acid.
3 Chemical Name and CAS Registry Number
Ethanolic acid [64-19-7]
4 Empirical Formula and Molecular Weight
C2H4O2 60.05
Functional Category
Acidifying agent.
Applications in Pharmaceutical Formulations or Technology Glacial and diluted acetic acid solutions are widely used as acidifying agents in a variety of pharmaceutical formulations and food preparations. Acetic acid is used in pharmaceutical products as a buffer system when combined with an acetate salt such as sodium acetate. Acetic acid is also claimed to have some antibacterial and antifungal properties.
Description
Glacial acetic acid occurs as a crystalline mass or a clear, colorless volatile solution with a pungent odor.Description Glacial acetic acid occurs as a crystalline mass or a clear, colorless volatile solution with a pungent odor.
Typical Properties
Acidity/alkalinity
pH = 2.4 (1M aqueous solution);
pH = 2.9 (0.1M aqueous solution);
pH = 3.4 (0.01M aqueous solution).
Boiling point is 1188C
Dissociation constant pKa = 4.76
Flash point 398C (closed cup); 578C (open cup).
Melting point 178C
Refractive index n D
20 = 1.3718
Solubility Miscible with ethanol, ether, glycerin, water, and other fixed and volatile oils.
Specific gravity is 1.045
Stability and Storage Conditions
Acetic acid should be stored in an airtight container in a cool, dry place.
Incompatibilities
Acetic acid reacts with alkaline substances.
Method of Manufacture
Acetic acid is usually made by one of three routes: acetaldehyde oxidation, involving direct air or oxygen oxidation of liquid acetaldehyde in the presence of manganese acetate, cobalt acetate, or copper acetate; liquid-phase oxidation of butane or naphtha; methanol carbonylation using a variety of techniques.
Safety
Acetic acid is widely used in pharmaceutical applications primarily to adjust the pH of formulations and is thus generally regarded as relatively nontoxic and nonirritant. However, glacial acetic acid or solutions containing over 50% w/w acetic acid in water or organic
solvents are considered corrosive and can cause damage to skin, eyes, nose, and mouth. If swallowed glacial acetic acid causes severe gastric irritation similar to that caused by hydrochloric acid.
(1) Dilute acetic acid solutions containing up to 10% w/w of acetic acid have been used topically following jellyfish stings.
(2) Dilute acetic acid solutions containing up to 5% w/w of acetic acid have also been applied topically to treat wounds and burns infected with Pseudomonas aeruginosa.
(3) The lowest lethal oral dose of glacial acetic acid in humans is reported to be 1470 mg/kg.
(4) The lowest lethal concentration on inhalation in humans is reported to be 816 ppm.Humans, are, however, estimated to consume approximately 1 g/day of acetic acid from the diet.
LD50 (mouse, IV): 0.525 g/kg(4)
LD50 (rabbit, skin): 1.06 g/kg
LD50 (rat, oral): 3.31 g/kg
Handling Precautions
Observe normal precautions appropriate to the circumstances and quantity of material handled. Acetic acid, particularly glacial acetic acid, can cause burns on contact with the skin, eyes, and mucous membranes. Splashes should be washed with copious quantities of water. Protective clothing, gloves, and eye protection are recommended.
Regulatory Status
GRAS listed. Accepted as a food additive in Europe. Included in the FDA Inactive Ingredients Database (injections, nasal, ophthalmic,and oral preparations). Included in parenteral and nonparenteral preparations licensed in the UK.
Related Substances
Acetic acid; artificial vinegar; dilute acetic acid.
Acetic acid
Comments: A diluted solution of glacial acetic acid containing 30–37% w/w of acetic acid.
Artificial vinegar
Comments: A solution containing 4% w/w of acetic acid.
Dilute acetic acid
Comments: A weak solution of acetic acid which may contain between 6–10% w/w of acetic acid.
In addition to glacial acetic acid, many pharmacopeias contain monographs for diluted acetic acid solutions of various strengths. For example, the USP32–NF27 has a monograph for acetic acid, which is defined as an acetic acid solution containing 36.0–37.0% w/w of acetic acid. Similarly, the BP 2009 contains separate monographs for glacial acetic acid, acetic acid (33%), and acetic acid (6%). Acetic acid (33%) BP 2009 contains 32.5–33.5% w/w of acetic acid. Acetic acid (6%) BP 2009 contains 5.7–6.3% w/w of acetic acid. The JP XV also contains a monograph for acetic acid that specifies that it contains 30.0–32.0% w/w of acetic acid. A specification for glacial acetic acid is contained in the Food Chemicals Codex (FCC). The EINECS number for acetic acid is 200-580-7. The PubChem Compound ID (CID) for glacial acetic acid is 176.
Sunday, March 27, 2011
Drugs and Biological Agents Used in Ophthalmic Surgery
Drugs and Biological Agents Used in Ophthalmic Surgery
ADJUNCTS IN ANTERIOR SEGMENT SURGERY Viscoelastic substances assist in ocular surgery by maintaining spaces, moving tissue, and protecting surfaces. These substances are
prepared from hyaluronate, chondroitin sulfate, or hydroxypropylmethylcellulose, share the following important physical characteristics: viscosity, shear flow, elasticity, cohesiveness, and coatability, and are broadly characterized as dispersive or cohesive. They are used almost exclusively in anterior segment surgery. Complications associated with viscoelastic substances are related to transient elevation of IOP after the procedure.
OPHTHALMIC GLUE Cyanoacrylate tissue adhesive (ISODENT, DERMABOND, HISTOACRYL),
while not FDA approved for the eye, is widely used in the management of corneal ulcerations and
1108 SECTION XIV Ophthalmology perforations. It is applied in liquid form and polymerized into a solid plug. Fibrinogen glue (TISSEEL) is increasingly being used on the ocular surface to secure tissue such as conjunctiva, amniotic membrane, and lamellar corneal grafts.
CORNEAL BAND KERATOPATHY Edetate disodium (disodium EDTA; ENDRATE) is a chelating agent that can be used to treat band keratopathy (i.e., a calcium deposit at the level of Bowman’s membrane on the cornea). After the overlying corneal epithelium is removed, it is
applied topically to chelate the calcium deposits from the cornea.
ANTERIOR SEGMENT GASES Sulfur hexafluoride (SF6) and perfluoropropane gases have long been used as vitreous substitutes during retinal surgery. In the anterior segment, they are
used in nonexpansile concentrations to treat Descemet’s detachments, typically after cataract surgery.
These detachments can cause mild-to-severe corneal edema. The gas is injected into the anterior
chamber to push Descemet’s membrane up against the stroma, where ideally it reattaches and
clears the corneal edema.
VITREOUS SUBSTITUTES The primary use of vitreous substitutes is reattachment of the
retina following vitrectomy and membrane-peeling procedures for complicated proliferative vitreoretinopathy and traction retinal detachments. Several compounds are available, including
gases, perfluorocarbon liquids, and silicone oil . With the exception of air, the gases expand because of interaction with systemic oxygen, carbon dioxide, and nitrogen, and this property makes them desirable to temporarily tamponade areas of the retina. However, use of these expansile gases carries the risk of complications from elevated IOP, subretinal gas, corneal edema, and cataract formation. The gases are absorbed over a time period of days (for air) to 2 months (for perfluoropropane).
The liquid perfluorocarbons, with specific gravities between 1.76 and 1.94, are denser than vitreous and are helpful in flattening the retina when vitreous is present. If a lens becomes dislocated into the vitreous, a perfluorocarbon liquid injection posteriorly will float the lens anteriorly, facilitating surgical retrieval. This liquid can be an important tool for flattening and unrolling severely detached and contorted retinas such as those found in giant retinal tears and proliferative vitreoretinopathy but are potentially toxic if it remains in chronic contact with the retina.
Silicone oil has had extensive use for long-term tamponade of the retina. Complications from
silicone oil use include glaucoma, cataract formation, corneal edema, corneal band keratopathy, and retinal toxicity.
ADJUNCTS IN ANTERIOR SEGMENT SURGERY Viscoelastic substances assist in ocular surgery by maintaining spaces, moving tissue, and protecting surfaces. These substances are
prepared from hyaluronate, chondroitin sulfate, or hydroxypropylmethylcellulose, share the following important physical characteristics: viscosity, shear flow, elasticity, cohesiveness, and coatability, and are broadly characterized as dispersive or cohesive. They are used almost exclusively in anterior segment surgery. Complications associated with viscoelastic substances are related to transient elevation of IOP after the procedure.
OPHTHALMIC GLUE Cyanoacrylate tissue adhesive (ISODENT, DERMABOND, HISTOACRYL),
while not FDA approved for the eye, is widely used in the management of corneal ulcerations and
1108 SECTION XIV Ophthalmology perforations. It is applied in liquid form and polymerized into a solid plug. Fibrinogen glue (TISSEEL) is increasingly being used on the ocular surface to secure tissue such as conjunctiva, amniotic membrane, and lamellar corneal grafts.
CORNEAL BAND KERATOPATHY Edetate disodium (disodium EDTA; ENDRATE) is a chelating agent that can be used to treat band keratopathy (i.e., a calcium deposit at the level of Bowman’s membrane on the cornea). After the overlying corneal epithelium is removed, it is
applied topically to chelate the calcium deposits from the cornea.
ANTERIOR SEGMENT GASES Sulfur hexafluoride (SF6) and perfluoropropane gases have long been used as vitreous substitutes during retinal surgery. In the anterior segment, they are
used in nonexpansile concentrations to treat Descemet’s detachments, typically after cataract surgery.
These detachments can cause mild-to-severe corneal edema. The gas is injected into the anterior
chamber to push Descemet’s membrane up against the stroma, where ideally it reattaches and
clears the corneal edema.
VITREOUS SUBSTITUTES The primary use of vitreous substitutes is reattachment of the
retina following vitrectomy and membrane-peeling procedures for complicated proliferative vitreoretinopathy and traction retinal detachments. Several compounds are available, including
gases, perfluorocarbon liquids, and silicone oil . With the exception of air, the gases expand because of interaction with systemic oxygen, carbon dioxide, and nitrogen, and this property makes them desirable to temporarily tamponade areas of the retina. However, use of these expansile gases carries the risk of complications from elevated IOP, subretinal gas, corneal edema, and cataract formation. The gases are absorbed over a time period of days (for air) to 2 months (for perfluoropropane).
The liquid perfluorocarbons, with specific gravities between 1.76 and 1.94, are denser than vitreous and are helpful in flattening the retina when vitreous is present. If a lens becomes dislocated into the vitreous, a perfluorocarbon liquid injection posteriorly will float the lens anteriorly, facilitating surgical retrieval. This liquid can be an important tool for flattening and unrolling severely detached and contorted retinas such as those found in giant retinal tears and proliferative vitreoretinopathy but are potentially toxic if it remains in chronic contact with the retina.
Silicone oil has had extensive use for long-term tamponade of the retina. Complications from
silicone oil use include glaucoma, cataract formation, corneal edema, corneal band keratopathy, and retinal toxicity.
Cardiopulmonary Arrest
Cardiopulmonary Arrest
INTRODUCTION
Cardiopulmonary arrest is the abrupt cessation of spontaneous and
effective ventilation and circulation following a cardiac or respiratory
event.1 CPR provides artificial ventilation and circulation until
it is possible to provide advanced cardiac life support (ACLS) and
reestablish spontaneous circulation. In the United States, there are
more than 460,000 victims of sudden cardiac arrest each year with
most occurring outside the hospital. The annual incidence of
sudden cardiac arrest has been estimated to be approximately 0.55
per 1,000 population and in the United States, sudden cardiac death
represents up to 15% of total mortality.
Early attempts at resuscitation date back to the biblical era.8
Modern-day resuscitation began in the late 1950s when it was
discovered that expired air delivered via a mouth-to-mouth technique
can maintain adequate oxygenation of blood.9 Later, in 1960,
Kouwenhoven and colleagues described “closed chest cardiac massage,”
and together with mouth-to-mouth ventilation, modern-day
CPR was born.
EPIDEMIOLOGY
In an adult patient, cardiopulmonary arrest usually results from the
development of an arrhythmia. Most cardiac arrests take place
outside the hospital, and most patients have underlying acute or
chronic heart disease. In more than two-thirds of patients, cardiac
arrest occurs as the first manifested clinical event with no preceding
symptoms or warning. Although the most common arrhythmia is
either VF or PVT, the number of patients with out-of-hospital
cardiac arrests presenting with VF as the initial rhythm has changed
dramatically.
In one study, the number of patients with VF was
61% in 1980 compared with only 41% in 2000, a reduction of
greater than 30%. A similar trend was noted with in-hospital
cardiac arrest as one study reported the number of patients presenting
with VF or PVT as the initial rhythm to be only 23%. Hospital
survival for in-hospital cardiac arrest related to VF or PVT is
approximately 36% with 75% having a good neurologic outcome.
Survival for out-of-hospital cardiac arrest caused by VF or PVT is
25% to 40%, with higher survival rates being observed in communities
that have a rapid response system.
In contrast to adult patients, only 15% of pediatric patients
present with VF or PVT as the initial rhythm. This is probably
because most pediatric arrests are respiratory-related as opposed to
the primary cardiac etiology seen in adult patients. Unfortunately,
survival following pediatric out-of-hospital cardiopulmonary arrest
ranges only from 2% to 10%, with most survivors having a poor
neurologic status.
ETIOLOGY
The most common cause of cardiopulmonary arrest in adult
patients is an acute myocardial infarction (MI) or pulmonary
embolism (PE) representing more than 70% of victims. In pediatric
patients, conversely, cardiopulmonary arrest is often the terminal
event of progressive shock or respiratory failure. The cause of
cardiac arrest varies with age, the underlying health of the child, and
the location of the event. Out-of-hospital arrests frequently are
associated with events such as trauma, sudden infant death syndrome,
drowning, poisoning, choking, severe asthma, and pneumonia.
In-hospital pediatric arrests are associated with sepsis,
respiratory failure, drug toxicity, metabolic disorders, and arrhythmias.
Pediatric out-of-hospital arrest generally presents with
hypoxia and hypercarbia progressing to respiratory arrest and
bradycardia and finally to asystolic cardiac arrest.
CLINICAL PRESENTATION
Symptoms
■ Anxiety, change in mental status or unconscious
■ Cold, clammy extremities
■ Dyspnea, shortness of breath or no respiration
■ Chest pain
■ Diaphoresis
■ Nausea and vomiting
Signs
■ Hypotension
■ Tachycardia, bradycardia, irregular or no pulse
■ Cyanosis
■ Hypothermia
■ Distant or absent heart and lung sounds
INTRODUCTION
Cardiopulmonary arrest is the abrupt cessation of spontaneous and
effective ventilation and circulation following a cardiac or respiratory
event.1 CPR provides artificial ventilation and circulation until
it is possible to provide advanced cardiac life support (ACLS) and
reestablish spontaneous circulation. In the United States, there are
more than 460,000 victims of sudden cardiac arrest each year with
most occurring outside the hospital. The annual incidence of
sudden cardiac arrest has been estimated to be approximately 0.55
per 1,000 population and in the United States, sudden cardiac death
represents up to 15% of total mortality.
Early attempts at resuscitation date back to the biblical era.8
Modern-day resuscitation began in the late 1950s when it was
discovered that expired air delivered via a mouth-to-mouth technique
can maintain adequate oxygenation of blood.9 Later, in 1960,
Kouwenhoven and colleagues described “closed chest cardiac massage,”
and together with mouth-to-mouth ventilation, modern-day
CPR was born.
EPIDEMIOLOGY
In an adult patient, cardiopulmonary arrest usually results from the
development of an arrhythmia. Most cardiac arrests take place
outside the hospital, and most patients have underlying acute or
chronic heart disease. In more than two-thirds of patients, cardiac
arrest occurs as the first manifested clinical event with no preceding
symptoms or warning. Although the most common arrhythmia is
either VF or PVT, the number of patients with out-of-hospital
cardiac arrests presenting with VF as the initial rhythm has changed
dramatically.
In one study, the number of patients with VF was
61% in 1980 compared with only 41% in 2000, a reduction of
greater than 30%. A similar trend was noted with in-hospital
cardiac arrest as one study reported the number of patients presenting
with VF or PVT as the initial rhythm to be only 23%. Hospital
survival for in-hospital cardiac arrest related to VF or PVT is
approximately 36% with 75% having a good neurologic outcome.
Survival for out-of-hospital cardiac arrest caused by VF or PVT is
25% to 40%, with higher survival rates being observed in communities
that have a rapid response system.
In contrast to adult patients, only 15% of pediatric patients
present with VF or PVT as the initial rhythm. This is probably
because most pediatric arrests are respiratory-related as opposed to
the primary cardiac etiology seen in adult patients. Unfortunately,
survival following pediatric out-of-hospital cardiopulmonary arrest
ranges only from 2% to 10%, with most survivors having a poor
neurologic status.
ETIOLOGY
The most common cause of cardiopulmonary arrest in adult
patients is an acute myocardial infarction (MI) or pulmonary
embolism (PE) representing more than 70% of victims. In pediatric
patients, conversely, cardiopulmonary arrest is often the terminal
event of progressive shock or respiratory failure. The cause of
cardiac arrest varies with age, the underlying health of the child, and
the location of the event. Out-of-hospital arrests frequently are
associated with events such as trauma, sudden infant death syndrome,
drowning, poisoning, choking, severe asthma, and pneumonia.
In-hospital pediatric arrests are associated with sepsis,
respiratory failure, drug toxicity, metabolic disorders, and arrhythmias.
Pediatric out-of-hospital arrest generally presents with
hypoxia and hypercarbia progressing to respiratory arrest and
bradycardia and finally to asystolic cardiac arrest.
CLINICAL PRESENTATION
Symptoms
■ Anxiety, change in mental status or unconscious
■ Cold, clammy extremities
■ Dyspnea, shortness of breath or no respiration
■ Chest pain
■ Diaphoresis
■ Nausea and vomiting
Signs
■ Hypotension
■ Tachycardia, bradycardia, irregular or no pulse
■ Cyanosis
■ Hypothermia
■ Distant or absent heart and lung sounds
Microemulsions
Microemulsions
Microemulsions are clear, stable, isotropic liquid mixtures of oil, water and surfactant, frequently in combination with a cosurfactant. The aqueous phase may contain salt(s) and/or other ingredients, and the "oil" may actually be a complex mixture of different hydrocarbons andolefins. In contrast to ordinary emulsions, microemulsions form upon simple mixing of the components and do not require the high shearconditions generally used in the formation of ordinary emulsions. The two basic types of microemulsions are direct (oil dispersed in water, o/w) and reversed (water dispersed in oil, w/o).
In ternary systems such as microemulsions, where two immiscible phases (water and ‘oil’) are present with a surfactant, the surfactantmolecules may form a monolayer at the interface between the oil and water, with the hydrophobic tails of the surfactant molecules dissolved in the oil phase and the hydrophilic head groups in the aqueous phase. As in the binary systems (water/surfactant or oil/surfactant), self-assembled structures of different types can be formed, ranging, for example, from (inverted) spherical and cylindrical micelles to lamellarphases and bicontinuous microemulsions, which may coexist with predominantly oil or aqueous phases.
Theory
Various theories concerning microemulsion formation, stability and phase behavior have been proposed over the years. For example, one explanation for their thermodynamic stability is that the oil/water dispersion is stabilized by the surfactant present and their formation involves the elastic properties of the surfactant film at the oil/water interface, which involves as parameters, the curvature and the rigidity of the film. These parameters may have an assumed or measured pressure and/or temperature dependence (and/or the salinity of the aqueous phase), which may be used to infer the region of stability of the microemulsion, or to delineate the region where three coexisting phases occur, for example. Calculations of the interfacial tension of the microemulsion with a coexisting oil or aqueous phase are also often of special focus and may sometimes be used to guide their formulation.
Newtonian fluid
A simple equation to describe Newtonian fluid behaviour is
T = μ.du/dy
where
τ is the shear stress exerted by the fluid ("drag") [Pa]
μ is the fluid viscosity - a constant of proportionality [Pa•s]
du/dy is the velocity gradient perpendicular to the direction of shear, or equivalently the strain rate [s−1]
Microemulsions are clear, stable, isotropic liquid mixtures of oil, water and surfactant, frequently in combination with a cosurfactant. The aqueous phase may contain salt(s) and/or other ingredients, and the "oil" may actually be a complex mixture of different hydrocarbons andolefins. In contrast to ordinary emulsions, microemulsions form upon simple mixing of the components and do not require the high shearconditions generally used in the formation of ordinary emulsions. The two basic types of microemulsions are direct (oil dispersed in water, o/w) and reversed (water dispersed in oil, w/o).
In ternary systems such as microemulsions, where two immiscible phases (water and ‘oil’) are present with a surfactant, the surfactantmolecules may form a monolayer at the interface between the oil and water, with the hydrophobic tails of the surfactant molecules dissolved in the oil phase and the hydrophilic head groups in the aqueous phase. As in the binary systems (water/surfactant or oil/surfactant), self-assembled structures of different types can be formed, ranging, for example, from (inverted) spherical and cylindrical micelles to lamellarphases and bicontinuous microemulsions, which may coexist with predominantly oil or aqueous phases.
Theory
Various theories concerning microemulsion formation, stability and phase behavior have been proposed over the years. For example, one explanation for their thermodynamic stability is that the oil/water dispersion is stabilized by the surfactant present and their formation involves the elastic properties of the surfactant film at the oil/water interface, which involves as parameters, the curvature and the rigidity of the film. These parameters may have an assumed or measured pressure and/or temperature dependence (and/or the salinity of the aqueous phase), which may be used to infer the region of stability of the microemulsion, or to delineate the region where three coexisting phases occur, for example. Calculations of the interfacial tension of the microemulsion with a coexisting oil or aqueous phase are also often of special focus and may sometimes be used to guide their formulation.
Newtonian fluid
A simple equation to describe Newtonian fluid behaviour is
T = μ.du/dy
where
τ is the shear stress exerted by the fluid ("drag") [Pa]
μ is the fluid viscosity - a constant of proportionality [Pa•s]
du/dy is the velocity gradient perpendicular to the direction of shear, or equivalently the strain rate [s−1]
Instability
Instability
There are three types of instability: flocculation, creaming, and coalescence. Flocculation describes the process by which the dispersed phase comes out of suspension in flakes. Coalescence is another form of instability, which describes when small droplets combine to form progressively larger ones. Emulsions can also undergo creaming, the migration of one of the substances to the top (or the bottom, depending on the relative densities of the two phases) of the emulsion under the influence of buoyancy or centripetal force when a centrifuge is used.
Surface active substances (surfactants) can increase the kinetic stability of emulsions greatly so that, once formed, the emulsion does not change significantly over years of storage. A Non-Ionic surfactant solution can become self-contained under the force of its own surface tension, remaining in the shape of its previous container for some time after the container is removed. Superfluids flow with zero friction and can escape their containers; an ionic solution tends to retain its current shape.
“Emulsion stability refers to the ability of an emulsion to resist change in its properties over time.”
There are three types of instability: flocculation, creaming, and coalescence. Flocculation describes the process by which the dispersed phase comes out of suspension in flakes. Coalescence is another form of instability, which describes when small droplets combine to form progressively larger ones. Emulsions can also undergo creaming, the migration of one of the substances to the top (or the bottom, depending on the relative densities of the two phases) of the emulsion under the influence of buoyancy or centripetal force when a centrifuge is used.
Surface active substances (surfactants) can increase the kinetic stability of emulsions greatly so that, once formed, the emulsion does not change significantly over years of storage. A Non-Ionic surfactant solution can become self-contained under the force of its own surface tension, remaining in the shape of its previous container for some time after the container is removed. Superfluids flow with zero friction and can escape their containers; an ionic solution tends to retain its current shape.
“Emulsion stability refers to the ability of an emulsion to resist change in its properties over time.”
Purification of Colloids
Purification of Colloids
Colloidal solution obtained from various methods is not pure. Therefore solution needs to be purified before it can be put to further use. Dialysis and Ultra-filtration techniques are used for purification of colloids.
Dialysis
We know that colloidal particles cannot be passed through parchment paper. This property is used in dialysis. The colloidal solution kept in parchment bag is dipped in beaker containing water, so that impurities may pass into aqueous medium leaving the colloidal particles inside the bag. The aqueous solution is renewed on timely basis to avoid rediffusion of impurities back into parchment bag. Pure colloidal solution is left inside the parchment paper. To make this process faster process of electrolysis in which two electrodes are dipped in the solvent and electric field is applied. The entire process is called electro-dialysis. The same process is used for purification of blood in case of kidney failure.
Ultra-Filtration
We know that ordinary filter paper cannot be used to filter out colloidal particles as pore size of filter paper are almost equal to size of colloidal particles. The separation of solute from colloidal system can be carried out by using ultra filter which have small pore size as compared to ordinary filter. Filtration using ultra papers is known as ultra filtration.
The pores of normal filter paper can be made smaller by soaking the filter paper in a solution of gelatin or colloidon and subsequently hardening them by soaking in formaldehyde. This decreases the pore size of filter paper which would restrict the colloidal particle to pass through it. By using a series of graded ultra filter paper, it is possible to separate colloidal particles of different sizes.
It is important to note that above methods to purify colloidal solution do not produce 100% solution. Absolute purity is not required as well as traces of small amount of electrolytes (impurities) are necessary for stability of colloidal solution.
Colloidal solution obtained from various methods is not pure. Therefore solution needs to be purified before it can be put to further use. Dialysis and Ultra-filtration techniques are used for purification of colloids.
Dialysis
We know that colloidal particles cannot be passed through parchment paper. This property is used in dialysis. The colloidal solution kept in parchment bag is dipped in beaker containing water, so that impurities may pass into aqueous medium leaving the colloidal particles inside the bag. The aqueous solution is renewed on timely basis to avoid rediffusion of impurities back into parchment bag. Pure colloidal solution is left inside the parchment paper. To make this process faster process of electrolysis in which two electrodes are dipped in the solvent and electric field is applied. The entire process is called electro-dialysis. The same process is used for purification of blood in case of kidney failure.
Ultra-Filtration
We know that ordinary filter paper cannot be used to filter out colloidal particles as pore size of filter paper are almost equal to size of colloidal particles. The separation of solute from colloidal system can be carried out by using ultra filter which have small pore size as compared to ordinary filter. Filtration using ultra papers is known as ultra filtration.
The pores of normal filter paper can be made smaller by soaking the filter paper in a solution of gelatin or colloidon and subsequently hardening them by soaking in formaldehyde. This decreases the pore size of filter paper which would restrict the colloidal particle to pass through it. By using a series of graded ultra filter paper, it is possible to separate colloidal particles of different sizes.
It is important to note that above methods to purify colloidal solution do not produce 100% solution. Absolute purity is not required as well as traces of small amount of electrolytes (impurities) are necessary for stability of colloidal solution.
PROPERTIES OF COLLOIDALS
PROPERTIES OF COLLOIDALS
The main characteristic properties of colloidal solutions are as follows.
(1) Physical properties
(i) Heterogeneous nature : Colloidal sols are heterogeneousin nature. They consists of two phases; the dispersed phase and the dispersion medium.
(ii) Stable nature : The colloidal solutions are quite stable. Their particles are in a state of motion and do not settle down at the bottom of the container.
(iii) Filterability : Colloidal particles are readily passed through the ordinary filter papers. However they can be retained by special filters known as ultrafilters (parchment paper).
(2) Colligative properties
(i) Due to formation of associated molecules, observed values of colligative properties like relative decrease in vapour pressure, elevation in boiling point, depression in freezing point, osmotic pressure are smaller than expected.
(ii) For a given colloidal sol the number of particles will be very small as compared to the true solution.
(3) Mechanical properties
(i) Brownian movement
(a) Robert Brown, a botanist discovered in 1827that the pollen grains suspended in water do not remain at rest but move about continuously and randomly in all directions.
(b) Later on, it was observed that the colloidal particles are moving at random in a zig – zag motion. This type of motion is called Brownian movement.
(c) The molecules of the dispersion medium are constantly colloiding with the particles of the dispersed phase. It was stated by Wiener in 1863that the impacts of the dispersion medium particles are unequal, thus causing a zig-zag motion of the dispersed phase particles.
(d) The Brownian movement explains the force of gravity acting on colloidal particles. This helps in providing stability to colloidal sols by not allowing them to settle down.
(ii) Diffusion : The sol particles diffuse from higher concentration to lower concentration region. However, due to bigger size, they diffuse at a lesser speed.
(iii) Sedimentation : The colloidal particles settle down under the influence of gravity at a very slow rate. This phenomenon is used for determining the molecular mass of the macromolecules.
(4) Optical properties : Tyndall effect
(i) When light passes through a sol, its path becomes visible because of scattering of light by particles. It is called Tyndall effect. This phenomenon was studied for the first time by Tyndall. The illuminated path of the beam is called Tyndall cone.
(ii) The intensity of the scattered light depends on the difference between the refractive indices of the dispersed phase and the dispersion medium.
(iii) In lyophobic colloids, the difference is appreciable and, therefore, the Tyndall effect is well - defined. But in lyophilic sols, the difference is very small and the Tyndall effect is very weak.
(iv) The Tyndall effect confirms the heterogeneous nature of the colloidal solution.
(v) The Tyndall effect has also been observed by an instrument called ultra – microscope.
Some example of Tyndall effect are as follows
(a) Tail of comets is seen as a Tyndall cone due to the scattering of light by the tiny solid particles left by the comet in its path.
(b) Due to scattering the sky looks blue.
(c) The blue colour of water in the sea is due to scattering of blue light by water molecules.
(d) Visibility of projector path and circus light.
(e) Visibility of sharp ray of sunlight passing through a slit in dark room.
(5) Electrical properties of Colloidals
(i) Electrophoresis
(a) The phenomenon of movement of colloidal particles under an applied electric field is calledelectrophoresis.
(b) If the particles accumulate near the negative electrode, the charge on the particles is positive.
(c) On the other hand, if the sol particles accumulate near the positive electrode, the charge on the particles is negative.
(d) The apparatus consists of a U-tube with two Pt-electrodes in each limb.
(e) When electrophoresis of a sol is carried out with out stirring, the bottom layer gradually becomes more concentrated while the top layer which contain pure and concentrated colloidal solution may be decanted. This is called electro decanation and is used for the purification as well as for concentrating the sol.
(f) The reverse of electrophoresis is called Sedimentation potential or Dorn effect. The sedimentation potential is setup when a particle is forced to move in a resting liquid. This phenomenon was discovered by Dorn and is also called Dorn effect.
(ii) Electrical double layer theory
(a) The electrical properties of colloids can also be explained by electrical double layer theory. According to this theory a double layer of ions appear at the surface of solid.
(b) The ion preferentially adsorbed is held in fixed part and imparts charge to colloidal particles.
(c) The second part consists of a diffuse mobile layer of ions. This second layer consists of both the type of charges. The net charge on the second layer is exactly equal to that on the fixed part.
(d) The existence of opposite sign on fixed and diffuse parts of double layer leads to appearance of a difference of potential, known as zeta potential or electrokinetic potential. Now when electric field is employed the particles move (electrophoresis)
(iii) Electro-osmosis
(a) In it the movement of the dispersed particles are prevented from moving by semipermeable membrane.
(b) Electro-osmosis is a phenomenon in which dispersion medium is allowed to move under the influence of an electrical field, whereas colloidal particles are not allowed to move.
(c) The existence of electro-osmosis has suggested that when liquid forced through a porous material or a capillary tube, a potential difference is setup between the two sides called as streaming potential. So the reverse of electro-osmosis is called streaming potential.
The main characteristic properties of colloidal solutions are as follows.
(1) Physical properties
(i) Heterogeneous nature : Colloidal sols are heterogeneousin nature. They consists of two phases; the dispersed phase and the dispersion medium.
(ii) Stable nature : The colloidal solutions are quite stable. Their particles are in a state of motion and do not settle down at the bottom of the container.
(iii) Filterability : Colloidal particles are readily passed through the ordinary filter papers. However they can be retained by special filters known as ultrafilters (parchment paper).
(2) Colligative properties
(i) Due to formation of associated molecules, observed values of colligative properties like relative decrease in vapour pressure, elevation in boiling point, depression in freezing point, osmotic pressure are smaller than expected.
(ii) For a given colloidal sol the number of particles will be very small as compared to the true solution.
(3) Mechanical properties
(i) Brownian movement
(a) Robert Brown, a botanist discovered in 1827that the pollen grains suspended in water do not remain at rest but move about continuously and randomly in all directions.
(b) Later on, it was observed that the colloidal particles are moving at random in a zig – zag motion. This type of motion is called Brownian movement.
(c) The molecules of the dispersion medium are constantly colloiding with the particles of the dispersed phase. It was stated by Wiener in 1863that the impacts of the dispersion medium particles are unequal, thus causing a zig-zag motion of the dispersed phase particles.
(d) The Brownian movement explains the force of gravity acting on colloidal particles. This helps in providing stability to colloidal sols by not allowing them to settle down.
(ii) Diffusion : The sol particles diffuse from higher concentration to lower concentration region. However, due to bigger size, they diffuse at a lesser speed.
(iii) Sedimentation : The colloidal particles settle down under the influence of gravity at a very slow rate. This phenomenon is used for determining the molecular mass of the macromolecules.
(4) Optical properties : Tyndall effect
(i) When light passes through a sol, its path becomes visible because of scattering of light by particles. It is called Tyndall effect. This phenomenon was studied for the first time by Tyndall. The illuminated path of the beam is called Tyndall cone.
(ii) The intensity of the scattered light depends on the difference between the refractive indices of the dispersed phase and the dispersion medium.
(iii) In lyophobic colloids, the difference is appreciable and, therefore, the Tyndall effect is well - defined. But in lyophilic sols, the difference is very small and the Tyndall effect is very weak.
(iv) The Tyndall effect confirms the heterogeneous nature of the colloidal solution.
(v) The Tyndall effect has also been observed by an instrument called ultra – microscope.
Some example of Tyndall effect are as follows
(a) Tail of comets is seen as a Tyndall cone due to the scattering of light by the tiny solid particles left by the comet in its path.
(b) Due to scattering the sky looks blue.
(c) The blue colour of water in the sea is due to scattering of blue light by water molecules.
(d) Visibility of projector path and circus light.
(e) Visibility of sharp ray of sunlight passing through a slit in dark room.
(5) Electrical properties of Colloidals
(i) Electrophoresis
(a) The phenomenon of movement of colloidal particles under an applied electric field is calledelectrophoresis.
(b) If the particles accumulate near the negative electrode, the charge on the particles is positive.
(c) On the other hand, if the sol particles accumulate near the positive electrode, the charge on the particles is negative.
(d) The apparatus consists of a U-tube with two Pt-electrodes in each limb.
(e) When electrophoresis of a sol is carried out with out stirring, the bottom layer gradually becomes more concentrated while the top layer which contain pure and concentrated colloidal solution may be decanted. This is called electro decanation and is used for the purification as well as for concentrating the sol.
(f) The reverse of electrophoresis is called Sedimentation potential or Dorn effect. The sedimentation potential is setup when a particle is forced to move in a resting liquid. This phenomenon was discovered by Dorn and is also called Dorn effect.
(ii) Electrical double layer theory
(a) The electrical properties of colloids can also be explained by electrical double layer theory. According to this theory a double layer of ions appear at the surface of solid.
(b) The ion preferentially adsorbed is held in fixed part and imparts charge to colloidal particles.
(c) The second part consists of a diffuse mobile layer of ions. This second layer consists of both the type of charges. The net charge on the second layer is exactly equal to that on the fixed part.
(d) The existence of opposite sign on fixed and diffuse parts of double layer leads to appearance of a difference of potential, known as zeta potential or electrokinetic potential. Now when electric field is employed the particles move (electrophoresis)
(iii) Electro-osmosis
(a) In it the movement of the dispersed particles are prevented from moving by semipermeable membrane.
(b) Electro-osmosis is a phenomenon in which dispersion medium is allowed to move under the influence of an electrical field, whereas colloidal particles are not allowed to move.
(c) The existence of electro-osmosis has suggested that when liquid forced through a porous material or a capillary tube, a potential difference is setup between the two sides called as streaming potential. So the reverse of electro-osmosis is called streaming potential.
Saturday, March 26, 2011
Chemical Classification
Chemical Classification
The crude drugs are divided into different groups according to the chemical nature of their most important constituent. Since the pharmacological activity and therapeutic significance of crude drugs are based on the nature of their chemical constituents.
The chemical classification of drugs is dependent upon the grouping of drugs with identical constituents.
An out of this classification is as follows:
1. Carbohydrates– Carbohydrates are polyhydroxy aldehydes or ketones containing an unbroken chain of carbon atoms.
Gums - Acacia, Tragacanth, Guargum
Mucilages - Plantago seed
Others - Starch, Honey, Agar, Pectin, Cotton
2. Glycosides – Glycosides are compounds which upon hydrolysis give rise to one or more sugars (glycone) and non-sugar (aglycone).
Anthraquinone Glycosides- Aloe, Cascara, Rhubarb, Senna
Saponins Glycosides- Quillaia, Arjuna, Glycyrrhiza
Cyanophore Glycosides- Wild cherry bark
Isothiocyanate Glycosides- Mustard
Cardiac Glycosides- Digitalis, Strophantus
Bitter Glycosides- Gentian, Calumba, Quassia, Chirata, Kalmegh
3. Tannins– Tannins are complex organic, non-nitrogenous derivatives of polyhydroxy benzoic acids. Examples- Pale catechu, Black catechu, Ashoka bark, Galls, Myrobalan, Bahera, Amla
4. Volatile oils– Monoterpenes and sesquiterpenes obtained from plants. Examples- Cinnamon, Fennel, Dill, Caraway, Coriander, Cardamom, Orange peel, Mint, Clove, valerian
5. Lipids Fixed oils – Castor, Olive, Almond, Shark liver oil Fats – Theobroma, Lanolin Waxes – Beeswax, Spermaceti
6. Resins– Complex mixture of compounds like resinols, resin acids, resinotannols, resenes. Examples Colophony, Podophyllum, Cannabis, Jalap, Capsicum, Turmeric, Balsam of Tolu and Peru, Asafoetida, Myrrh, Ginger
7. Alkaloids – Nitrogenous substance of plant origin Pyridine and Piperidine – Lobelia, Nicotiana Tropane - Coca, Belladonna, Datura, Stramonium, Hyoscyamus, Henbane Quinoline – Cinchona Isoquinoline – Opium, Ipecac, Calumba Indole – Ergot, Rauwolfia Amines – Ephedra Purina – Tea, coffee
8. Protein – Gelatin, Ficin, Papain
9. Vitamins - Yeast
10. Triterpenes – Rasna, Colocynth
Merits : It is a popular approach for phytochemical studies
Demerits: Ambiguities arise when particular drugs possess a number of compounds belonging to different groups of compounds.
Chemotaxonomic Classification
This system of classification relies on the chemical similarity of a taxon i.e. it is based on the existence of relationship between constituents in various plants. There are certain types of chemical constituents that characterize certain classes of plants. This gives birth to entirely new concept of chemotaxonomy that utilizes chemical facts/characters for understanding the taxonomical status, relationships and the evolution of the plants. For example, tropane alkaloids generally occur among the members of Solanaceae thereby, serving as a chemotaxonomic marker. Similarly other secondary plant metabolites can serve as the basis of classification of crude drugs. The berberine alkaloid in Berberis and Argemone; Rutin in Rutaceae members, ranunculaceous alkaloids among its members etc are other examples.
It is the latest system of classification and gives more scope for understanding the relationship between chemical constituents, their biosynthesis and their possible action.
The crude drugs are divided into different groups according to the chemical nature of their most important constituent. Since the pharmacological activity and therapeutic significance of crude drugs are based on the nature of their chemical constituents.
The chemical classification of drugs is dependent upon the grouping of drugs with identical constituents.
An out of this classification is as follows:
1. Carbohydrates– Carbohydrates are polyhydroxy aldehydes or ketones containing an unbroken chain of carbon atoms.
Gums - Acacia, Tragacanth, Guargum
Mucilages - Plantago seed
Others - Starch, Honey, Agar, Pectin, Cotton
2. Glycosides – Glycosides are compounds which upon hydrolysis give rise to one or more sugars (glycone) and non-sugar (aglycone).
Anthraquinone Glycosides- Aloe, Cascara, Rhubarb, Senna
Saponins Glycosides- Quillaia, Arjuna, Glycyrrhiza
Cyanophore Glycosides- Wild cherry bark
Isothiocyanate Glycosides- Mustard
Cardiac Glycosides- Digitalis, Strophantus
Bitter Glycosides- Gentian, Calumba, Quassia, Chirata, Kalmegh
3. Tannins– Tannins are complex organic, non-nitrogenous derivatives of polyhydroxy benzoic acids. Examples- Pale catechu, Black catechu, Ashoka bark, Galls, Myrobalan, Bahera, Amla
4. Volatile oils– Monoterpenes and sesquiterpenes obtained from plants. Examples- Cinnamon, Fennel, Dill, Caraway, Coriander, Cardamom, Orange peel, Mint, Clove, valerian
5. Lipids Fixed oils – Castor, Olive, Almond, Shark liver oil Fats – Theobroma, Lanolin Waxes – Beeswax, Spermaceti
6. Resins– Complex mixture of compounds like resinols, resin acids, resinotannols, resenes. Examples Colophony, Podophyllum, Cannabis, Jalap, Capsicum, Turmeric, Balsam of Tolu and Peru, Asafoetida, Myrrh, Ginger
7. Alkaloids – Nitrogenous substance of plant origin Pyridine and Piperidine – Lobelia, Nicotiana Tropane - Coca, Belladonna, Datura, Stramonium, Hyoscyamus, Henbane Quinoline – Cinchona Isoquinoline – Opium, Ipecac, Calumba Indole – Ergot, Rauwolfia Amines – Ephedra Purina – Tea, coffee
8. Protein – Gelatin, Ficin, Papain
9. Vitamins - Yeast
10. Triterpenes – Rasna, Colocynth
Merits : It is a popular approach for phytochemical studies
Demerits: Ambiguities arise when particular drugs possess a number of compounds belonging to different groups of compounds.
Chemotaxonomic Classification
This system of classification relies on the chemical similarity of a taxon i.e. it is based on the existence of relationship between constituents in various plants. There are certain types of chemical constituents that characterize certain classes of plants. This gives birth to entirely new concept of chemotaxonomy that utilizes chemical facts/characters for understanding the taxonomical status, relationships and the evolution of the plants. For example, tropane alkaloids generally occur among the members of Solanaceae thereby, serving as a chemotaxonomic marker. Similarly other secondary plant metabolites can serve as the basis of classification of crude drugs. The berberine alkaloid in Berberis and Argemone; Rutin in Rutaceae members, ranunculaceous alkaloids among its members etc are other examples.
It is the latest system of classification and gives more scope for understanding the relationship between chemical constituents, their biosynthesis and their possible action.
Classification of Crude Drugs
Classification of Crude Drugs
The most important natural sources of drugs are higher plant, microbes and animals and marine organisms. Some useful products are obtained from minerals that are both organic and inorganic in nature. In order to pursue (or to follow) the study of the individual drugs, one must adopt some particular sequence of arrangement and this is referred to a system of classification of drugs.
A method of classification should be
(a) Simple
(b) Easy to use (
c) Free from confusion and ambiguities.
Because of their wide distribution, each arrangement of classification has its own merits and demerits, but for the purpose of study the drugs are classified in the following different ways: 1. Alphabetical classification
2. Morphological classification
3. Taxonomic classification
4. Pharmacological classification
5. Chemical classification
6. Chemotaxonomical
classification Alphabetical Classification Alphabetical classification is the simplest way of classification of any disconnected items. Crude drugs are arranged in alphabetical order of their Latin and English names (common names) or sometimes local language names (vernacular names).
Some of the pharmacopoeias, dictionaries and reference books which classify crude drugs according to this system are as follows.
1. Indian Pharmacopoeia
2. British Pharmacopoeia
3. British Herbal Pharmacopoeia
4. United States Pharmacopoeia and National Formulary
5. British Pharmaceutical Codex.
6. European Pharmacopoeia
In European Pharmacopoeia these are arranged according to their names in Latin where in U.S.P. and B.P.C., these are arranged in English.
Merits:
• It is easy and quick to use
• There is no repetition of entries and is devoid of confusion.
• In this system location, tracing and addition of drug entries is easy.
Demerits:
There is no relationship between previous and successive drug entries. Examples: Acacia, Benzoin, Cinchona, Dill, Ergot, Fennel, Gentian, Hyoscyamus, Ipecacuanha, Jalap, Kurchi, Liquorice, Mints, Nuxvomica, Opium, Podophyllum, Quassia, Rauwolfia, Senna, Vasaka, Wool fat, Yellow bees wax, Zeodary.
Morphological Classification
In this system, the drugs are arranged according to the morphological or external characters of the plant parts or animal parts i.e. which part of the plant is used as a drug e. g. leaves, roots, stem etc. The drugs obtained from the direct parts of the plants and containing cellular tissues are called as organized drugs e. g. Rhizomes, barks, leaves, fruits, entire plants, hairs and fibres.
The drugs which are prepared from plants by some intermediate physical processes such as incision, drying or extraction with a solvent and not containing any cellular plant tissues are called as unorganized drugs. Aloe juice, opium latex, agar, gambir, gelatin, tragacanth, benzoin, honey, beeswax, lemon grass oil etc. are examples of unorganized drugs.
Organised Drugs
Woods– Quassia, Sandalwood, Red Sandalwood.
Leaves– Digitalis, Eucalyptus, Gymnema, Mint, Senna, Spearmint, Squill, Tulsi, Vasaka, Coca,Buchu, Hamamelis, Hyoscyamus, Belladonna, Tea.
Barks– Arjuna, Ashoka, Cascara, Cassia, Cinchona, Cinnamon, Kurchi, Quillia, Wild cherry.
Flowering parts– Clove, Pyrethrum, Saffron, Santonica, Chamomile.
Fruits– Amla, Anise, Bael, Bahera, Bitter Orange peel, Capsicum, Caraway, Cardamom, Colocynth, Coriander, Cumin, Dill, Fennel, Gokhru, Hirda, Lemon peel, Senna pod, Star anise, Tamarind, Vidang.
Seeds– Bitter almond, Black Mustard, Cardamom, Colchicum, Ispaghula, Kaladana, Linseed, Nutmeg, Nux vomica, Physostigma, Psyllium, Strophanthus, White mustard.
Roots and Rhizomes– Aconite, Ashwagandha, Calamus, Calumba, Colchicum corm, Dioscorea, Galanga, Garlic, Gention, Ginger, Ginseng, Glycyrrhiza, Podophyllum, Ipecac, Ipomoea, Jalap, Jatamansi, Rauwolfia, Rhubarb, Sassurea, Senega, Shatavari, Turmeric, Valerian, Squill.
Plants and Herbs– Ergot, Ephedra, Bacopa, Andrographis, Kalmegh, Yeast, Vinca, Datura, Centella.
Hair and Fibres– Cotton, Hemp, Jute, Silk, Flax.
Unorganised Drugs.
Dried latex– Opium, Papain Dried Juice– Aloe, Kino Dried extracts– Agar, Alginate, Black catechu, Pale catechu, Pectin Waxes - Beeswax, Spermaceti, Carnauba wax Gums – Acacia, Guar Gum, Indian Gum, Sterculia, Tragacenth.
Resins– Asafoetida, Benzoin, Colophony, copaiba Guaiacum, Guggul, Mastic, Coal tar, Tar, Tolu balsam, Storax, Sandarac.
Volatile oil– Turpentine, Anise, Coriander, Peppermint, Rosemary, Sandalwood, Cinnamon, Lemon, Caraway, Dill, Clove, Eucalyptus, Nutmeg, Camphor.
Fixed oils and Fats– Arachis, Castor, Chalmoogra, Coconut, Cotton seed, Linseed, Olive, Sesame, Almond, Theobroma, Cod-liver, Halibut liver, Kokum butter.
Animal Products – Bees wax, Cantharides, Cod-liver oil, Gelatin, Halibut liver oil, Honey, Shark liver oil, shellac, Spermaceti wax, wool fat, musk, Lactose.
Fossil organism and Minerals– Bentonite, Kaolin, Kiesslguhr, Talc.
The most important natural sources of drugs are higher plant, microbes and animals and marine organisms. Some useful products are obtained from minerals that are both organic and inorganic in nature. In order to pursue (or to follow) the study of the individual drugs, one must adopt some particular sequence of arrangement and this is referred to a system of classification of drugs.
A method of classification should be
(a) Simple
(b) Easy to use (
c) Free from confusion and ambiguities.
Because of their wide distribution, each arrangement of classification has its own merits and demerits, but for the purpose of study the drugs are classified in the following different ways: 1. Alphabetical classification
2. Morphological classification
3. Taxonomic classification
4. Pharmacological classification
5. Chemical classification
6. Chemotaxonomical
classification Alphabetical Classification Alphabetical classification is the simplest way of classification of any disconnected items. Crude drugs are arranged in alphabetical order of their Latin and English names (common names) or sometimes local language names (vernacular names).
Some of the pharmacopoeias, dictionaries and reference books which classify crude drugs according to this system are as follows.
1. Indian Pharmacopoeia
2. British Pharmacopoeia
3. British Herbal Pharmacopoeia
4. United States Pharmacopoeia and National Formulary
5. British Pharmaceutical Codex.
6. European Pharmacopoeia
In European Pharmacopoeia these are arranged according to their names in Latin where in U.S.P. and B.P.C., these are arranged in English.
Merits:
• It is easy and quick to use
• There is no repetition of entries and is devoid of confusion.
• In this system location, tracing and addition of drug entries is easy.
Demerits:
There is no relationship between previous and successive drug entries. Examples: Acacia, Benzoin, Cinchona, Dill, Ergot, Fennel, Gentian, Hyoscyamus, Ipecacuanha, Jalap, Kurchi, Liquorice, Mints, Nuxvomica, Opium, Podophyllum, Quassia, Rauwolfia, Senna, Vasaka, Wool fat, Yellow bees wax, Zeodary.
Morphological Classification
In this system, the drugs are arranged according to the morphological or external characters of the plant parts or animal parts i.e. which part of the plant is used as a drug e. g. leaves, roots, stem etc. The drugs obtained from the direct parts of the plants and containing cellular tissues are called as organized drugs e. g. Rhizomes, barks, leaves, fruits, entire plants, hairs and fibres.
The drugs which are prepared from plants by some intermediate physical processes such as incision, drying or extraction with a solvent and not containing any cellular plant tissues are called as unorganized drugs. Aloe juice, opium latex, agar, gambir, gelatin, tragacanth, benzoin, honey, beeswax, lemon grass oil etc. are examples of unorganized drugs.
Organised Drugs
Woods– Quassia, Sandalwood, Red Sandalwood.
Leaves– Digitalis, Eucalyptus, Gymnema, Mint, Senna, Spearmint, Squill, Tulsi, Vasaka, Coca,Buchu, Hamamelis, Hyoscyamus, Belladonna, Tea.
Barks– Arjuna, Ashoka, Cascara, Cassia, Cinchona, Cinnamon, Kurchi, Quillia, Wild cherry.
Flowering parts– Clove, Pyrethrum, Saffron, Santonica, Chamomile.
Fruits– Amla, Anise, Bael, Bahera, Bitter Orange peel, Capsicum, Caraway, Cardamom, Colocynth, Coriander, Cumin, Dill, Fennel, Gokhru, Hirda, Lemon peel, Senna pod, Star anise, Tamarind, Vidang.
Seeds– Bitter almond, Black Mustard, Cardamom, Colchicum, Ispaghula, Kaladana, Linseed, Nutmeg, Nux vomica, Physostigma, Psyllium, Strophanthus, White mustard.
Roots and Rhizomes– Aconite, Ashwagandha, Calamus, Calumba, Colchicum corm, Dioscorea, Galanga, Garlic, Gention, Ginger, Ginseng, Glycyrrhiza, Podophyllum, Ipecac, Ipomoea, Jalap, Jatamansi, Rauwolfia, Rhubarb, Sassurea, Senega, Shatavari, Turmeric, Valerian, Squill.
Plants and Herbs– Ergot, Ephedra, Bacopa, Andrographis, Kalmegh, Yeast, Vinca, Datura, Centella.
Hair and Fibres– Cotton, Hemp, Jute, Silk, Flax.
Unorganised Drugs.
Dried latex– Opium, Papain Dried Juice– Aloe, Kino Dried extracts– Agar, Alginate, Black catechu, Pale catechu, Pectin Waxes - Beeswax, Spermaceti, Carnauba wax Gums – Acacia, Guar Gum, Indian Gum, Sterculia, Tragacenth.
Resins– Asafoetida, Benzoin, Colophony, copaiba Guaiacum, Guggul, Mastic, Coal tar, Tar, Tolu balsam, Storax, Sandarac.
Volatile oil– Turpentine, Anise, Coriander, Peppermint, Rosemary, Sandalwood, Cinnamon, Lemon, Caraway, Dill, Clove, Eucalyptus, Nutmeg, Camphor.
Fixed oils and Fats– Arachis, Castor, Chalmoogra, Coconut, Cotton seed, Linseed, Olive, Sesame, Almond, Theobroma, Cod-liver, Halibut liver, Kokum butter.
Animal Products – Bees wax, Cantharides, Cod-liver oil, Gelatin, Halibut liver oil, Honey, Shark liver oil, shellac, Spermaceti wax, wool fat, musk, Lactose.
Fossil organism and Minerals– Bentonite, Kaolin, Kiesslguhr, Talc.
Storage Conditions
Storage Conditions
In general, a drug product should be evaluated under storage conditions (with appropriate
tolerances) that test its thermal stability and, if applicable, its sensitivity to moisture or
potential for solvent loss. The storage conditions and the lengths of studies chosen should be
sufficient to cover storage, shipment, and subsequent use.
Stability testing of the drug product after constitution or dilution, if applicable, should be
conducted to provide information for the labeling on the preparation, storage condition, and
in-use period of the constituted or diluted product. This testing should be performed on the
constituted or diluted product through the proposed in-use period on primary batches as part
of the formal stability studies at initial and final time points and, if full shelf life long term
data will not be available before submission, at 12 months or the last time point for which
data will be available. In general, this testing need not be repeated on commitment batches.
The long term testing should cover a minimum of 12 months’ duration on at least three
primary batches at the time of submission and should be continued for a period of time
sufficient to cover the proposed shelf life. Additional data accumulated during the assessment
period of the registration application should be submitted to the authorities if requested. Data
from the accelerated storage condition and, if appropriate, from the intermediate storage
condition can be used to evaluate the effect of short term excursions outside the label storage
conditions (such as might occur during shipping).
Long term, accelerated, and, where appropriate, intermediate storage conditions for drug
products are detailed in the sections below. The general case applies if the drug product is not
specifically covered by a subsequent section. Alternative storage conditions can be used, if
justified.
In general, a drug product should be evaluated under storage conditions (with appropriate
tolerances) that test its thermal stability and, if applicable, its sensitivity to moisture or
potential for solvent loss. The storage conditions and the lengths of studies chosen should be
sufficient to cover storage, shipment, and subsequent use.
Stability testing of the drug product after constitution or dilution, if applicable, should be
conducted to provide information for the labeling on the preparation, storage condition, and
in-use period of the constituted or diluted product. This testing should be performed on the
constituted or diluted product through the proposed in-use period on primary batches as part
of the formal stability studies at initial and final time points and, if full shelf life long term
data will not be available before submission, at 12 months or the last time point for which
data will be available. In general, this testing need not be repeated on commitment batches.
The long term testing should cover a minimum of 12 months’ duration on at least three
primary batches at the time of submission and should be continued for a period of time
sufficient to cover the proposed shelf life. Additional data accumulated during the assessment
period of the registration application should be submitted to the authorities if requested. Data
from the accelerated storage condition and, if appropriate, from the intermediate storage
condition can be used to evaluate the effect of short term excursions outside the label storage
conditions (such as might occur during shipping).
Long term, accelerated, and, where appropriate, intermediate storage conditions for drug
products are detailed in the sections below. The general case applies if the drug product is not
specifically covered by a subsequent section. Alternative storage conditions can be used, if
justified.
Safety Pharmacology Studies for Human Pharmaceuticals
Safety Pharmacology Studies for Human Pharmaceuticals
physiological functions in relation to exposure in the therapeutic range and above. (See Note 2 for definitions of primary pharmacodynamic and secondary pharmacodynamic studies.) In some cases, information on the primary and secondary pharmacodynamic properties of the substance may contribute to the safety evaluation for potential adverse effect(s) in humans and should be considered along with the findings of safety pharmacology studies. 2. GUIDELINE 2.1 Objectives of Studies The objectives of safety pharmacology studies are: 1) to identify undesirable pharmacodynamic properties of a substance that may have relevance to its human safety; 2) to evaluate adverse pharmacodynamic and/or pathophysiological effects of a substance observed in toxicology and/or clinical studies; and 3) to investigate the mechanism of the adverse pharmacodynamic effects observed and/or suspected. The investigational plan to meet these objectives should be clearly identified and delineated. 2.2 General Considerations in Selection and Design of Safety Pharmacology Studies Since pharmacological effects vary depending on the specific properties of each test substance, the studies should be selected and designed accordingly. The following factors should be considered (the list is not comprehensive): 1) Effects related to the therapeutic class of the test substance, since the mechanism of action may suggest specific adverse effects (e.g., proarrhythmia is a common feature of antiarrhythmic agents); 2) Adverse effects associated with members of the chemical or therapeutic class, but independent of the primary pharmacodynamic effects (e.g., anti-psychotics and QT prolongation); 3) Ligand binding or enzyme assay data suggesting a potential for adverse effects; 4) Results from previous safety pharmacology studies, from secondary pharmacodynamic studies, from toxicology studies, or from human use that warrant further investigation to establish and characterize the relevance of these findings to potential adverse effects in humans. During early development, sufficient information (e.g., comparative metabolism) may not always be available to rationally select or design the studies in accordance with the points stated above; in such circumstances, a more general approach in safety pharmacology investigations can be applied. A hierarchy of organ systems can be developed according to their importance with respect to life-supporting functions. Vital organs or systems, the functions of which are acutely critical for life, such as the cardiovascular, respiratory and central nervous systems, are considered to be the most important ones to assess in safety pharmacology studies. Other organ systems, such as the renal or gastrointestinal system, the functions of which can be transiently disrupted by adverse pharmacodynamic effects without causing irreversible harm, are of less immediate investigative concern. Safety pharmacology evaluation of effects on these other systems may be of particular importance when considering factors such as the likely clinical trial or patient population (e.g. gastrointestinal tract in Crohn’s disease, renal function in primary renal hypertension, immune system in immunocompromised patients.).
physiological functions in relation to exposure in the therapeutic range and above. (See Note 2 for definitions of primary pharmacodynamic and secondary pharmacodynamic studies.) In some cases, information on the primary and secondary pharmacodynamic properties of the substance may contribute to the safety evaluation for potential adverse effect(s) in humans and should be considered along with the findings of safety pharmacology studies. 2. GUIDELINE 2.1 Objectives of Studies The objectives of safety pharmacology studies are: 1) to identify undesirable pharmacodynamic properties of a substance that may have relevance to its human safety; 2) to evaluate adverse pharmacodynamic and/or pathophysiological effects of a substance observed in toxicology and/or clinical studies; and 3) to investigate the mechanism of the adverse pharmacodynamic effects observed and/or suspected. The investigational plan to meet these objectives should be clearly identified and delineated. 2.2 General Considerations in Selection and Design of Safety Pharmacology Studies Since pharmacological effects vary depending on the specific properties of each test substance, the studies should be selected and designed accordingly. The following factors should be considered (the list is not comprehensive): 1) Effects related to the therapeutic class of the test substance, since the mechanism of action may suggest specific adverse effects (e.g., proarrhythmia is a common feature of antiarrhythmic agents); 2) Adverse effects associated with members of the chemical or therapeutic class, but independent of the primary pharmacodynamic effects (e.g., anti-psychotics and QT prolongation); 3) Ligand binding or enzyme assay data suggesting a potential for adverse effects; 4) Results from previous safety pharmacology studies, from secondary pharmacodynamic studies, from toxicology studies, or from human use that warrant further investigation to establish and characterize the relevance of these findings to potential adverse effects in humans. During early development, sufficient information (e.g., comparative metabolism) may not always be available to rationally select or design the studies in accordance with the points stated above; in such circumstances, a more general approach in safety pharmacology investigations can be applied. A hierarchy of organ systems can be developed according to their importance with respect to life-supporting functions. Vital organs or systems, the functions of which are acutely critical for life, such as the cardiovascular, respiratory and central nervous systems, are considered to be the most important ones to assess in safety pharmacology studies. Other organ systems, such as the renal or gastrointestinal system, the functions of which can be transiently disrupted by adverse pharmacodynamic effects without causing irreversible harm, are of less immediate investigative concern. Safety pharmacology evaluation of effects on these other systems may be of particular importance when considering factors such as the likely clinical trial or patient population (e.g. gastrointestinal tract in Crohn’s disease, renal function in primary renal hypertension, immune system in immunocompromised patients.).
ADSORPTION
ADSORPTION
Adsorption is a process that occurs when a gas or liquid solute accumulates on the surface
of a solid or a liquid (adsorbent), forming a molecular or atomic film (the adsorbate). It is
different from absorption, in which a substance diffuses into a liquid or solid to form a
solution. The term sorption encompasses both processes, while desorption is the reverse
process.
Adsorption is operative in most natural physical, biological, and chemical systems, and is
widely used in industrial applications such as activated charcoal, synthetic resins and water
purification.
Similar to surface tension, adsorption is a consequence of surface energy. In a bulk
material, all the bonding requirements (be they ionic, covalent or metallic) of the
constituent atoms of the material are filled. But atoms on the (clean) surface experience a
bond deficiency, because they are not wholly surrounded by other atoms. Thus it is
energetically favourable for them to bond with whatever happens to be available. The exact
nature of the bonding depends on the details of the species involved, but the adsorbed
material is generally classified as exhibiting physisorption or chemisorption.
Physisorption or physical adsorption is a type of adsorption in which the adsorbate
adheres to the surface only through Van der Waals (weak intermolecular) interactions,
which are also responsible for the non-ideal behaviour of real gases.
Chemisorption is a type of adsorption whereby a molecule adheres to a surface through
the formation of a chemical bond, as opposed to the Van der Waals forces which cause
physisorption.
Adsorption is usually described through isotherms, that is, functions which connect the
amount of adsorbate on the adsorbent, with its pressure (if gas) or concentration (if liquid).
One can find in literature several models describing process of adsorption, namely
Freundlich isotherm, Langmuir isotherm, BET isotherm, etc. We will deal with Langmuir
isotherm in more details:
Langmuir isotherm
In 1916, Irving Langmuir published an isotherm for gases adsorbed on solids, which
retained his name. It is an empirical isotherm derived from a proposed kinetic mechanism.
It is based on four hypotheses:
1. The surface of the adsorbent is uniform, that is, all the adsorption sites are equal.
2. Adsorbed molecules do not interact.
3. All adsorption occurs through the same mechanism.
4. At the maximum adsorption, only a monolayer is formed: molecules of adsorbate
do not deposit on other, already adsorbed, molecules of adsorbate, only on the free
surface of the adsorbent.
For liquids (adsorbate) adsorbed on solids (adsorbent), the Langmuir isotherm
Adsorption is a process that occurs when a gas or liquid solute accumulates on the surface
of a solid or a liquid (adsorbent), forming a molecular or atomic film (the adsorbate). It is
different from absorption, in which a substance diffuses into a liquid or solid to form a
solution. The term sorption encompasses both processes, while desorption is the reverse
process.
Adsorption is operative in most natural physical, biological, and chemical systems, and is
widely used in industrial applications such as activated charcoal, synthetic resins and water
purification.
Similar to surface tension, adsorption is a consequence of surface energy. In a bulk
material, all the bonding requirements (be they ionic, covalent or metallic) of the
constituent atoms of the material are filled. But atoms on the (clean) surface experience a
bond deficiency, because they are not wholly surrounded by other atoms. Thus it is
energetically favourable for them to bond with whatever happens to be available. The exact
nature of the bonding depends on the details of the species involved, but the adsorbed
material is generally classified as exhibiting physisorption or chemisorption.
Physisorption or physical adsorption is a type of adsorption in which the adsorbate
adheres to the surface only through Van der Waals (weak intermolecular) interactions,
which are also responsible for the non-ideal behaviour of real gases.
Chemisorption is a type of adsorption whereby a molecule adheres to a surface through
the formation of a chemical bond, as opposed to the Van der Waals forces which cause
physisorption.
Adsorption is usually described through isotherms, that is, functions which connect the
amount of adsorbate on the adsorbent, with its pressure (if gas) or concentration (if liquid).
One can find in literature several models describing process of adsorption, namely
Freundlich isotherm, Langmuir isotherm, BET isotherm, etc. We will deal with Langmuir
isotherm in more details:
Langmuir isotherm
In 1916, Irving Langmuir published an isotherm for gases adsorbed on solids, which
retained his name. It is an empirical isotherm derived from a proposed kinetic mechanism.
It is based on four hypotheses:
1. The surface of the adsorbent is uniform, that is, all the adsorption sites are equal.
2. Adsorbed molecules do not interact.
3. All adsorption occurs through the same mechanism.
4. At the maximum adsorption, only a monolayer is formed: molecules of adsorbate
do not deposit on other, already adsorbed, molecules of adsorbate, only on the free
surface of the adsorbent.
For liquids (adsorbate) adsorbed on solids (adsorbent), the Langmuir isotherm
Saturday, March 5, 2011
Experience The Well Being Benefits Of Acai Plus
It is important for our bodies to receive the vitamins we need to keep good health. Nutritional vitamins and minerals can be found in our meals however we often don't obtain the suitable amounts by weight-reduction plan alone. It could be necessary to take supplemental nutritional vitamins to keep away from any deficiency.
Everybody has totally different needs because of their age, genes or lifestyle. Even a slight deficiency may cause health problems and cause you to feel bad and lose productivity. Lack of vitality, sleep disorders and mental fatigue can all be improved with supplemental vitamins.
The Acai Plus Drink
Acai Plus provides a delicious vitamin drink combined with over 100 dietary ingredients. The flavor comes from the wonderful Acai berry that's from the Brazilian rainforest in South America. This exceptional berry tastes like a blend of berry and chocolate. It is stuffed with antioxidants, amino acids, and essential fatty acids. The Brazilians think about it to have exceptional therapeutic and nutritional qualities.
The Acai fruit was featured on Oprah and other programs as a brilliant food. The liquid supplement Acai Plus contains this fruit together with goji and mangosteen extracts. These are all exotic fruits known to have extraordinary healing and nutritional values.
Delicious and Wholesome Fruits
The goji fruit is also thought-about a super food. It comes from the mountains of Tibet and Mongolia the place it grows wild. Native people harvest the berries in late summer time and bundle them to sell. They're fully freed from chemical pesticides because they develop in distant areas. It has lengthy been identified that folks in these areas have a longer life span than the remainder of world. It may very well be partly credited to their publicity to this fruit and different native meals they eat. It is mentioned to have a style mixture of a cranberry and cherry.
The mangosteen is a fruit from Southeast Asia. It has been utilized by native residents for hundreds of years to deal with health conditions. The xanthone rich rind is particularly valued as a folk medicine. It has a citrus taste with a touch of peach.
These scrumptious fruits give Acai Plus its incomparable taste. Most nutritional vitamins and supplemental drinks have a foul taste and leave an after taste in your mouth, but you will not expertise that with Acai Plus.
Everybody has totally different needs because of their age, genes or lifestyle. Even a slight deficiency may cause health problems and cause you to feel bad and lose productivity. Lack of vitality, sleep disorders and mental fatigue can all be improved with supplemental vitamins.
The Acai Plus Drink
Acai Plus provides a delicious vitamin drink combined with over 100 dietary ingredients. The flavor comes from the wonderful Acai berry that's from the Brazilian rainforest in South America. This exceptional berry tastes like a blend of berry and chocolate. It is stuffed with antioxidants, amino acids, and essential fatty acids. The Brazilians think about it to have exceptional therapeutic and nutritional qualities.
The Acai fruit was featured on Oprah and other programs as a brilliant food. The liquid supplement Acai Plus contains this fruit together with goji and mangosteen extracts. These are all exotic fruits known to have extraordinary healing and nutritional values.
Delicious and Wholesome Fruits
The goji fruit is also thought-about a super food. It comes from the mountains of Tibet and Mongolia the place it grows wild. Native people harvest the berries in late summer time and bundle them to sell. They're fully freed from chemical pesticides because they develop in distant areas. It has lengthy been identified that folks in these areas have a longer life span than the remainder of world. It may very well be partly credited to their publicity to this fruit and different native meals they eat. It is mentioned to have a style mixture of a cranberry and cherry.
The mangosteen is a fruit from Southeast Asia. It has been utilized by native residents for hundreds of years to deal with health conditions. The xanthone rich rind is particularly valued as a folk medicine. It has a citrus taste with a touch of peach.
These scrumptious fruits give Acai Plus its incomparable taste. Most nutritional vitamins and supplemental drinks have a foul taste and leave an after taste in your mouth, but you will not expertise that with Acai Plus.
Beware Of Food Additives
A food additive is any substance (not commonly regarded or used as food) which is used to modify a food’s chemical, physical, or organoleptic (affecting the senses) characteristics. It is commonly added to stabilize a product or to change the flavor, color, texture, or consistency of food items or as a preservative so that they retain their properties for longer periods of time. With an increase in the usage of food additives since the 19th century, there has been a great concern with regard to their safety in relation to human health. Today, there are scientific evidences that prove the link between the use of food additives and the development of various physical and mental disorders.
Saccharin and aspartame are the most commonly used sugar substitutes. They are added to beverages, diet sodas, or soft drinks and are used in the sweet food industry as sweetening agents. Research has shown that these food additives can result in birth defects, neurological imbalances, and even cancer. Overuse of saccharine has been associated with bladder cancer, while excess consumption of aspartame containing products has been related to skin and breathing problems, seizures, headaches, and mood disturbances.
Monosodium glutamate (MSG) is an additive that is often added to soups, sauces, frozen foods, and Chinese preparations to enhance the overall flavoring. But little do people know that eating too much of monosodium glutamate can damage the nerve cells of the body and cause frequent, throbbing headaches. Further, it has been found to elevate the risk of suffering from obesity, high blood pressure, and heart disorders.
Sodium nitrite and sodium nitrate are another form of preservatives, which are detrimental to health when consumed. Frequently used as a meat preservative, these are suspected to be one of the causes for stomach cancer. The nitrite present in the additive combines with a harmful compound to form nitrosamines – an extremely powerful cancer-causing chemical. Similarly, potassium bromate, usually used in breads and rolls, has been reported to increase the possibility of developing certain types of cancer.
Butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) are preservatives added to fats and oils to prevent them from getting oxidized and going rancid. These additives have been found to be carcinogenic. Therefore, consuming them in large amounts can actually trigger cancer. In addition, butylated hydroxyanisole has also been associated with the development of bronchial asthma, cholesterol imbalances, and hyperactivity. Reading the food labels of products before buying them is the best way of keeping away these unsavory additives. Moreover, going natural – eating more of fresh, whole organic foods, and cutting down on processed, canned, and packed products – can help you make your diet healthy.
Saccharin and aspartame are the most commonly used sugar substitutes. They are added to beverages, diet sodas, or soft drinks and are used in the sweet food industry as sweetening agents. Research has shown that these food additives can result in birth defects, neurological imbalances, and even cancer. Overuse of saccharine has been associated with bladder cancer, while excess consumption of aspartame containing products has been related to skin and breathing problems, seizures, headaches, and mood disturbances.
Monosodium glutamate (MSG) is an additive that is often added to soups, sauces, frozen foods, and Chinese preparations to enhance the overall flavoring. But little do people know that eating too much of monosodium glutamate can damage the nerve cells of the body and cause frequent, throbbing headaches. Further, it has been found to elevate the risk of suffering from obesity, high blood pressure, and heart disorders.
Sodium nitrite and sodium nitrate are another form of preservatives, which are detrimental to health when consumed. Frequently used as a meat preservative, these are suspected to be one of the causes for stomach cancer. The nitrite present in the additive combines with a harmful compound to form nitrosamines – an extremely powerful cancer-causing chemical. Similarly, potassium bromate, usually used in breads and rolls, has been reported to increase the possibility of developing certain types of cancer.
Butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) are preservatives added to fats and oils to prevent them from getting oxidized and going rancid. These additives have been found to be carcinogenic. Therefore, consuming them in large amounts can actually trigger cancer. In addition, butylated hydroxyanisole has also been associated with the development of bronchial asthma, cholesterol imbalances, and hyperactivity. Reading the food labels of products before buying them is the best way of keeping away these unsavory additives. Moreover, going natural – eating more of fresh, whole organic foods, and cutting down on processed, canned, and packed products – can help you make your diet healthy.
Tramadol Can Help You
Many people suffer from chronic pain, whether from a debilitating illness or from major surgery. This chronic pain can cause suffering that will affect a person’s everyday life. If you are one of these people dealing with such pain, then you know how difficult it can be to just get through daily life. You need a solution that will actually work. You need something more than a temporary solution to help ease the pain from time to time. Instead, you need a solution that will provide pain relief for the whole day so that you can get back to enjoying life again.
Is there such a solution out there? Up until now, you may not have thought so, and you may even have tried a medicine cabinet’s worth of medications with no real results. The good news is that there is a solution out there. If you have not considered it before, then you may want to think about Tramadol.
This medication is designed specifically to manage chronic pain for those who deal with such conditions. A strong, and long-lasting pain reliever available for the most part by prescription, is designed to offer total pain relief through the whole day for those who are dealing with past surgery pain or chronic conditions. Additionally, there are many other nuisance syndromes that can be rectified through Tramadol. These conditions include Restless Leg Syndrome (RLS), depression, anxiety, and even severe phobias.
If you are suffering from chronic pain or any of these conditions and Tramadol could provide treatment for them to offer you a better quality of life, then you will want to consider that you can purchase the medication for discounted prices online. Buying Tramadol online can be more simple for you and it can save you a great deal of money, since you will want to take the medication on a long term basis.
Many people suffer from chronic pain conditions that lead to a lowered quality of life. For these people, relief is necessary for them to be able to enjoy anything on their daily basis. This is why a genuine pain reliever like Tramadol can be, not only useful, but actually necessary. Before you try one more short term pain reliever that just will not work, consider how Tramadol can help you. You do not have to suffer a day longer. All you need to do is know that a long term option is out there.
Is there such a solution out there? Up until now, you may not have thought so, and you may even have tried a medicine cabinet’s worth of medications with no real results. The good news is that there is a solution out there. If you have not considered it before, then you may want to think about Tramadol.
This medication is designed specifically to manage chronic pain for those who deal with such conditions. A strong, and long-lasting pain reliever available for the most part by prescription, is designed to offer total pain relief through the whole day for those who are dealing with past surgery pain or chronic conditions. Additionally, there are many other nuisance syndromes that can be rectified through Tramadol. These conditions include Restless Leg Syndrome (RLS), depression, anxiety, and even severe phobias.
If you are suffering from chronic pain or any of these conditions and Tramadol could provide treatment for them to offer you a better quality of life, then you will want to consider that you can purchase the medication for discounted prices online. Buying Tramadol online can be more simple for you and it can save you a great deal of money, since you will want to take the medication on a long term basis.
Many people suffer from chronic pain conditions that lead to a lowered quality of life. For these people, relief is necessary for them to be able to enjoy anything on their daily basis. This is why a genuine pain reliever like Tramadol can be, not only useful, but actually necessary. Before you try one more short term pain reliever that just will not work, consider how Tramadol can help you. You do not have to suffer a day longer. All you need to do is know that a long term option is out there.
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