The Biopharmaceutics Classification System and Compounding Pharmacy, Part II
In Part I of this series, the Biopharmaceutics Classification System (BCS) was defined and the four biopharmaceutic drug classes were presented based upon their aqueous solubility and membrane permeability.
This classification scheme provides a basis for establishing in vitro-in vivo correlations. It also aids in estimating the absorption of drugs based on the fundamental dissolution and permeability properties of physiologic importance. It should be noted that dissolution media may be varied in the studies. Although there are additional factors to be considered, this system provides valuable information. Based upon flux equations and their derivations related to this system, the following can be stated1:
- If two drug products of the same drug have the same concentration time profile at the intestinal membrane surface, then they will have the same rate and extent of absorption.
- If two drug products have the same in vivo dissolution profile under all luminal conditions, they will have the same rate and extent of drug absorption.
Class I Drugs
In the case of immediate-release dosage forms with rapid dissolution of Class I drugs, the absorption rate is controlled by the gastric emptying rate. These generally will not pose a problem for compounding oral solid dosage forms, such as capsules, molded tablets, tablets, etc. Example drugs include:
Class II Drugs
Class II Drugs are dissolution-rate limited and the dissolution profiles must be clearly defined and reproducible. In compounding solid oral dosage forms, these may be considered for techniques to enhance their dissolution rate. Absorption of this class is generally slower than for Class I. Example drugs include:
- Valproic acid
Class III Drugs
Class III drugs are quite soluble and generally have rapid dissolution rates. If the dissolution rate is fast, then absorption is the rate-limiting step and may be variable due to variations in gastrointestinal transit, luminal content, and membrane permeability, rather than formulation factors. For compounding, the issue is not so much related to dissolution but to methods to enhance intestinal absorption. Example drugs include:
- Ascorbic acid
- Codeine phosphate
- Sodium cloxacillin
Class IV Drugs
Class IV drugs can have significant problems as they have low solubility and low permeability. Even though information about solubility, dose, and particle size may be available, information on the drugs' permeabilities are generally less available. Techniques can be considered regarding selection of excipients designed to enhance their dissolution rates and absorption. Example drugs are:
The primary purpose of the BCS and its use by the U.S. Food and Drug Administration is to assist in qualifying drug products for a waiver of in vivo bioequivalence studies; the objective of the BCS is to predict in vivo performance of drug products from in vitro measurements of permeability and solubility. The information can also be of assistance to compounding pharmacists when formulating compounded drug preparations.
- Amidon GL, Lennernäs H, Shah VP et al. A theoretical basis for a biopharmaceutic drug classification: The correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res 1995; 12(3): 413-420.
Loyd V. Allen, Jr., PhD, RPh
International Journal of Pharmaceutical Compounding
Remington: The Science and Practice of Pharmacy