Biopharmaceutics Classification System
Encyclopedia
The Biopharmaceutics Classification System is a guide for predicting the intestinal
drug
absorption provided by the U.S. Food and Drug Administration http://www.fda.gov/. The fundamental basis for the BCS was established by Dr. Gordon Amidon who was presented with a Distinguished Science Award at the August 2006 International Pharmaceutical Federation
(FIP) congress in Salvador, Brazil.
This system restricts the prediction using the parameters solubility
and intestinal permeability. The solubility
classification is based on a United States Pharmacopoeia (USP) aperture. The intestinal permeability classification is based on a comparison to the intravenous injection
. All those factors are highly important, since 85% of the most sold drugs in the USA and Europe
are orally administered
.
According to the Biopharmaceutics Classification System, drug substances are classified as follows:
The drugs are classified in BCS on the basis of following parameters:
1. Solubility
2. Permeability
3. Dissolution
The class boundaries for these parameters are:
1. Solubility class boundaries- It is based on the highest dose strength of an immediate release product. A drug is considered highly soluble when the highest dose strength is soluble in 250ml or less of aqueous media over the ph range of 1 to 7.5. The volume estimate of 250ml is derived from typical bioequivalence study protocols that prescribe administration of a drug product to fasting human volunteers with a glass of water.
2. Permeability class boundaries- It is based indirectly on the extent of absorption of a drug substance in humans and directly on the measurement of rates of mass transfer across human intestinal membrane. Alternatively non-human systems capable of prediction the drug absorption systems capable of predicting the drug absorption in humans can be used (such as in-vitro culture methods).
A drug substance is considered highly permeable when the extent of absorption in humans is determined to be 90 % or more of the administered dose based on a mass-balance determination or in comparison to and intravenous dose.
3. Dissolution class boundaries- An immediate release products is considered rapidly dissolving when no less than 85% of the labeled amount of the drug substance dissolve within 30 minutes using USP Dissolution Apparatus 1 at 100 RPM or Apparatus 2 at 50 RPM in a volume of 900ml or less in following media,) 0.1 N HCl or simulated gastric fluid or pH 4.5 buffer and pH 6.8 buffer or simulated intestinal fluid.
Gastrointestinal tract
The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
drug
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
absorption provided by the U.S. Food and Drug Administration http://www.fda.gov/. The fundamental basis for the BCS was established by Dr. Gordon Amidon who was presented with a Distinguished Science Award at the August 2006 International Pharmaceutical Federation
International Pharmaceutical Federation
The International Pharmaceutical Federation or Fédération Internationale Pharmaceutique, abbreviated as FIP, is an international federation of national organisations that represent pharmacists and pharmaceutical scientists...
(FIP) congress in Salvador, Brazil.
This system restricts the prediction using the parameters solubility
Solubility
Solubility is the property of a solid, liquid, or gaseous chemical substance called solute to dissolve in a solid, liquid, or gaseous solvent to form a homogeneous solution of the solute in the solvent. The solubility of a substance fundamentally depends on the used solvent as well as on...
and intestinal permeability. The solubility
Solubility
Solubility is the property of a solid, liquid, or gaseous chemical substance called solute to dissolve in a solid, liquid, or gaseous solvent to form a homogeneous solution of the solute in the solvent. The solubility of a substance fundamentally depends on the used solvent as well as on...
classification is based on a United States Pharmacopoeia (USP) aperture. The intestinal permeability classification is based on a comparison to the intravenous injection
Route of administration
A route of administration in pharmacology and toxicology is the path by which a drug, fluid, poison, or other substance is taken into the body.-Classification:Routes of administration are usually classified by application location...
. All those factors are highly important, since 85% of the most sold drugs in the USA and Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...
are orally administered
Route of administration
A route of administration in pharmacology and toxicology is the path by which a drug, fluid, poison, or other substance is taken into the body.-Classification:Routes of administration are usually classified by application location...
.
According to the Biopharmaceutics Classification System, drug substances are classified as follows:
- Class I - high permeability, high solubilitySolubilitySolubility is the property of a solid, liquid, or gaseous chemical substance called solute to dissolve in a solid, liquid, or gaseous solvent to form a homogeneous solution of the solute in the solvent. The solubility of a substance fundamentally depends on the used solvent as well as on...
- Example: metoprololMetoprololMetoprolol is a selective β1 receptor blocker used in treatment of several diseases of the cardiovascular system, especially hypertension. The active substance metoprolol is employed either as metoprolol succinate or metoprolol tartrate...
- Those compounds are well absorbed and their absorption rate is usually higher than excretion.
- Example: metoprolol
- Class II - high permeability, low solubility
- Example: glibenclamideGlibenclamideGlibenclamide , also known as glyburide , is an antidiabetic drug in a class of medications known as sulfonylureas, closely related to sulfa drugs...
- The bioavailabilityBioavailabilityIn pharmacology, bioavailability is a subcategory of absorption and is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered...
of those products is limited by their solvation rate. A correlation between the in vivoIn vivoIn vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...
bioavailability and the in vitroIn vitroIn vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
solvation can be found.
- Example: glibenclamide
- Class III - low permeability, high solubility
- Example: cimetidineCimetidineCimetidine INN is a histamine H2-receptor antagonist that inhibits the production of acid in the stomach. It is largely used in the treatment of heartburn and peptic ulcers. It is marketed by GlaxoSmithKline under the trade name Tagamet...
- The absorption is limited by the permeation rate but the drug is solvated very fast. If the formulation does not change the permeability or gastro-intestinal duration time, then class I criteria can be applied.
- Example: cimetidine
- Class IV - low permeability, low solubility
- Example: hydrochlorothiazideHydrochlorothiazideHydrochlorothiazide, abbreviated HCTZ, HCT, or HZT, is a first-line diuretic drug of the thiazide class that acts by inhibiting the kidneys' ability to retain water. This reduces the volume of the blood, decreasing blood return to the heart and thus cardiac output and, by other mechanisms, is...
- Those compounds have a poor bioavailability. Usually they are not well absorbed over the intestinal mucosa and a high variability is expected.
- Example: hydrochlorothiazide
The drugs are classified in BCS on the basis of following parameters:
1. Solubility
2. Permeability
3. Dissolution
The class boundaries for these parameters are:
1. Solubility class boundaries- It is based on the highest dose strength of an immediate release product. A drug is considered highly soluble when the highest dose strength is soluble in 250ml or less of aqueous media over the ph range of 1 to 7.5. The volume estimate of 250ml is derived from typical bioequivalence study protocols that prescribe administration of a drug product to fasting human volunteers with a glass of water.
2. Permeability class boundaries- It is based indirectly on the extent of absorption of a drug substance in humans and directly on the measurement of rates of mass transfer across human intestinal membrane. Alternatively non-human systems capable of prediction the drug absorption systems capable of predicting the drug absorption in humans can be used (such as in-vitro culture methods).
A drug substance is considered highly permeable when the extent of absorption in humans is determined to be 90 % or more of the administered dose based on a mass-balance determination or in comparison to and intravenous dose.
3. Dissolution class boundaries- An immediate release products is considered rapidly dissolving when no less than 85% of the labeled amount of the drug substance dissolve within 30 minutes using USP Dissolution Apparatus 1 at 100 RPM or Apparatus 2 at 50 RPM in a volume of 900ml or less in following media,) 0.1 N HCl or simulated gastric fluid or pH 4.5 buffer and pH 6.8 buffer or simulated intestinal fluid.
See also
- ADMEADMEADME is an acronym in pharmacokinetics and pharmacology for absorption, distribution, metabolism, and excretion, and describes the disposition of a pharmaceutical compound within an organism...
- Partition coefficientPartition coefficientIn chemistry and the pharmaceutical sciences, a partition- or distribution coefficient is the ratio of concentrations of a compound in the two phases of a mixture of two immiscible solvents at equilibrium. The terms "gas/liquid partition coefficient" and "air/water partition coefficient" are...
- BioavailabilityBioavailabilityIn pharmacology, bioavailability is a subcategory of absorption and is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered...
- Drug metabolismDrug metabolismDrug metabolism is the biochemical modification of pharmaceutical substances by living organisms, usually through specialized enzymatic systems. This is a form of xenobiotic metabolism. Drug metabolism often converts lipophilic chemical compounds into more readily excreted polar products...
- First pass effectFirst pass effectThe first-pass effect is a phenomenon of drug metabolism whereby the concentration of a drug is greatly reduced before it reaches the systemic circulation. It is the fraction of lost drug during the process of absorption which is generally related to the liver and gut wall...
- Partition coefficient
- Polar surface areaPolar surface areaThe polar surface area of a molecule is defined as the surface sum over all polar atoms, primarily oxygen and nitrogen, also including their attached hydrogens....
- IVIVCIVIVCAn In-vitro in-vivo correlation has been defined by the Food and Drug Administration as "a predictive mathematical model describing the relationship between an in-vitro property of a dosage form and an in-vivo response"....
External links
- BCS guidance of the U.S. Food and Drug Administration