The Biopharmaceutics Classification System is a system to differentiate the drugs on the basis of their solubility and permeability.[1]
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[citation needed].
BCS classes[edit]
Simulation design. Oral drug absorption was computed based on (approximating) the physicochemical, pharmacokinetic, and drug dissolution properties of the six selected BCS Class II drugs using the previously reported simulation method (Tsume and Amidon, 2010). The Biopharmaceutics Classification System (BCS) and the corresponding guidance issued by the FDA categorize drug substances into 4 groups based on aqueous solubility and intestinal membrane permeability (Amidon et al., 1995).The FDA BCS guidance allows biowaivers for BCS Class I drugs based on drug product in vitro dissolution. We evaluated 263 approved generic drugs of IR products listed on the WHO EML to find out the distribution of BCS Class 1, 2, 3, and 4 drugs in approved ANDA applications during the 2000 to 2011 period. The WHO EML was used as it is a publicly available list of Class 1, 2, 3, and 4 drugs. Of the 130 orally administered drugs on the WHO list, 61 could be classified with certainty. Twenty-one (84%) of these belong to class I (highly soluble, highly permeable), 10 (17%) to class II (poorly soluble, highly permeable), 24 (39%) to class III (highly soluble, poorly permeable) and 6 (10%) to class IV (poorly soluble, poorly permeable).
According to the Biopharmaceutical Classification System (BCS) drug substances are classified to four classes upon their solubility and permeability:[1]
- Class I - high permeability, high solubility
- Example: metoprolol, paracetamol[2]
- Those compounds are well absorbed and their absorption rate is usually higher than excretion.
- Class II - high permeability, low solubility
- Example: glibenclamide, bicalutamide, ezetimibe, aceclofenac
- 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: Bifonazole
- Those compounds have a poor bioavailability. Usually they are not well absorbed over the intestinal mucosa and a high variability is expected.
Definitions[edit]
The drugs are classified in BCS on the basis of solubility, permeability, and dissolution.
Solubility class boundaries are 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.
Permeability class boundaries are 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.
For 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 M HCl or simulated gastric fluid or pH 4.5 buffer and pH 6.8 buffer or simulated intestinal fluid.
See also[edit]
- ADME
References[edit]
- ^ abMehta M (2016). Biopharmaceutics Classification System (BCS): Development, Implementation, and Growth. Wiley. ISBN978-1-118-47661-1.
- ^'Draft agreement'(PDF). www.ema.europa.eu. 22 June 2017. Retrieved 2019-07-03.
Further reading[edit]
- Folkers G, van de Waterbeemd H, Lennernäs H, Artursson P, Mannhold R, Kubinyi H (2003). Drug Bioavailability: Estimation of Solubility, Permeability, Absorption and Bioavailability (Methods and Principles in Medicinal Chemistry). Weinheim: Wiley-VCH. ISBN3-527-30438-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. PMID7617530.
External links[edit]
- BCS guidance of the U.S. Food and Drug Administration
Bcs Classification Bcs Class 2 Drugs List
This new multidisciplinary guideline is proposed to address biopharmaceutics classification system (BCS)-based biowaivers. BCS-based biowaivers may be applicable to BCS Class I and III drugs, however BCS-based biowaivers for these two classes are not recognized worldwide. This means that pharmaceutical companies have to follow different approaches in the different regions. This guideline will provide recommendations to support the biopharmaceutics classification of medicinal products and will provide recommendations to support the waiver of bioequivalence studies. This will result in the harmonisation of current regional guidelines/guidance and support streamlined global drug development.
Keywords: Bioequivalence study exemptions, solubility, permeability, in vitro dissolution
