The Biopharmaceutics Classification System and Compounding Pharmacy, Part I
The Biopharmaceutic Drug Classification Defined
The Biopharmaceutic Drug Classification is a method of correlating the in vitro drug product dissolution and its in vivo bioavailability. It is based on the drugs SOLUBILITY and the drugs PERMEATION and is a method of estimating a drug's absorption/bioavailability. The rationale is to use the drugs dissolution and gastrointestinal permeability as fundamental parameters in controlling the rate and extent of drug absorption. Further, the processes can be influenced by the pH of the surrounding media, presence of biological surfactants, etc.
Four Biopharmaceutic Drug Classes
The system places a drug into one of four classes based upon its aqueous solubility and its permeability. These classes are Class I, Class II, Class III, and Class IV, as follows:
This can be placed in a 2 × 2 table as follows:
- High solubility-High permeability drugs
- Low solubility-High permeability drugs
- High solubility-Low permeability drugs
- Low solubility-Low permeability drugs
Characteristics of the Four Classes
High solubility relates to a rapid dissolution of the drug and high permeability relates to rapid absorption of the drug. So, a Class I drug dissolves quickly and is absorbed rapidly.
Low solubility can mean that solubility is a rate-limiting factor if the drug has high permeability. So, a Class II drug is limited by its rate of dissolution, but the amount that dissolves is rapidly absorbed.
High solubility and low permeability drugs will dissolve quickly but be limited by their rate of absorption. So, a Class III drug will dissolve rapidly but be absorbed slowly and is absorption rate-limited.
Low solubility and low permeability can be a problematic drug because they are limited both by their rate of dissolution and rate of absorption. These are the Class IV drugs
Generally, there will be minimal difficulties with bioavailability with Class I drugs. Class II drugs are dissolution-rate limited and may be considered for techniques to enhance their dissolution rate. Class III drugs are quite soluble, and their absorption rate may be the problem but may be approached from pH adjustments, surfactants, etc. Class IV drugs can be problematic as they are low solubility and low permeability and may require different methods to enhance their bioavailability. Interestingly enough, some dosage forms are specifically designed to address some of these issues where they contain methods and excipients designed to enhance their dissolution rates, etc.
Next month, we will look at drug examples in the four different classes and how they can be used by the compounding pharmacist.
Loyd V. Allen, Jr., PhD, RPh
International Journal of Pharmaceutical Compounding
Remington: The Science and Practice of Pharmacy