Biopharmaceutics Classification System

The Biopharmaceutics Classification System 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 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:

• 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
  • Example: glibenclamide
  • The bioavailability of those products is limited by their solvation rate. A correlation between the in vivo bioavailability and the in vitro solvation can be found.
• 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
  • Example: hydrochlorothiazide
  • Those compounds have a poor bioavailability. Usually they are not well absorbed over the intestinal mucosa and a high variability is expected.

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 15 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.