Biopharmaceutics Classification System
The Biopharmaceutics Classification System is a system to differentiate the drugs on the basis of their solubility and permeability. It is a guide for predicting the intestinal drug absorption provided by the U.S. Food and Drug Administration. The fundamental basis for the BCS was established by 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 because 85% of the most sold drugs in the United States and Europe are orally administered.
According to the Biopharmaceutics Classification System, drug substances are classified as follows:
- Class I - high permeability, high solubility
- Example: metoprolol
- Those compounds are well absorbed and their absorption rate is usually higher than excretion.
- Class II - high permeability, low solubility
- Class III - low permeability, high solubility
- Example: cimetidine
- 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.
- Class IV - low permeability, low solubility
The drugs are classified in BCS on the basis of following parameters:
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 250 ml or less of aqueous media over the pH range of 1 to 7.5. The volume estimate of 250 ml 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 predicting 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 an intravenous dose.
3. Dissolution class boundaries- An immediate release product is considered rapidly dissolving when no less than 85% of the labeled amount of the drug substance dissolves within 15 minutes using USP Dissolution Apparatus 1 at 100 RPM or Apparatus 2 at 50 RPM in a volume of 900 ml or less in the following media: 0.1 N HCl or simulated gastric fluid or pH 4.5 buffer and pH 6.8 buffer or simulated intestinal fluid.
- Polar surface area
- Gerd Folkers; Waterbeemd, Han van de; Lennernäs, Hans; Per Artursson; Raimund Mannhold; Hugo Kubinyi (2003). Drug Bioavailability : Estimation of Solubility, Permeability, Absorption and Bioavailability (Methods and Principles in Medicinal Chemistry). Weinheim: Wiley-VCH. ISBN 3-527-30438-X.
- Amidon GL, Lennernäs H, Shah VP, Crison JR (March 1995). "A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability". Pharm. Res. 12 (3): 413–20. PMID 7617530.