5.2 Biopharmaceutics Classification System:
The Biopharmaceutics Classification System (BCS) is a scientific framework for classification of APIs for oral administration. The BCS is based upon aqueous solubility and intestinal permeability. An API is considered highly soluble when the highest dose is soluble in 250 ml or less of aqueous media at 37 °C over the pH range 1.2–6.8. The volume estimate of 250 ml is derived from typical bioequivalence study protocols that prescribe administration of a medicine together with a glass of water to fasting human volunteers. A highly permeable API is absorbed orally to an extent of 85% or more of the administered dose based on a mass-balance determination or in comparison to an intravenous dose (19).
Hence an API can be classified as belonging to one of four classes:
■ Class 1 (high solubility, high permeability);
■ Class 2 (low solubility, high permeability);
■ Class 3 (high solubility, low permeability);
■ Class 4 (low solubility, low permeability).
Classification of APIs included in the WHO Model List of essential medicines is provided in the WHO Technical Report Series (20).
The BCS may be particularly helpful to assess the importance of aqueous solubility since it relates the solubility of the API to the unit dose. Aqueous solubility should not be a concern in the formulation of immediate-release dosage forms containing class 1 and 3 substances.
For class 2 substances, the effect of particle size, polymorphic form, and solubility enhancers, among others, should be considered, as the absorption of these substances may be limited by dissolution rate. The same applies to class 4 substances, although factors other than dissolution may also govern the
oral absorption. However, overall the BCS classification can be used as a basis when estimating the likelihood of different absorption of paediatric medicines when the dosage form and/or excipients used in adult medicines differ from those used for paediatric medicines.
In addition, for BCS class 3 and 4 substances, where the absorption process and/or intestinal first pass also restrict bioavailability, the possibility of excipients affecting transit time (efflux), transporter function and metabolic enzymes (typically CYP3A4) should be taken into consideration.
Development of Paediatric Medicines: points to consider in formulation,
(Annex 5, WHO Technical Report Series 970, 2012)
