Oral dosage form permeability

Next to permeability, aqueous solubility is the most important biopharmaceutical property associated with oral drug absorption. These two properties have established the basis for a biopharmaceutical classification system (BCS) and have become the subject of an FDA guidance entitled Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a... 

FDA s biopharmaceutics classification system, BCS [5], serves as a guide for in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms. BCS relies on two ADME properties, passive permeability and solu-... 

The BCS permits classification of drug substances based upon the key determinants of rate and extent of drug absorption from immediate release solid oral dosage forms—aqueous solubility, gastrointestinal permeability, and dissolution. The BCS provides four distinct classes of drug substances (http //www.fda.gov/ cder / guidance/3618fnl.pdf) ... 

The three major factors that determine the rate and extent of drug absorption from solid oral dosage forms are solubility, dissolution rate, and permeability. This is recognized in the BCS, which categorizes drugs into four classes based on their aqueous solubility and intestinal permeability (Table 4). 

Recently the FDA has proposed the waiver of bioequivalence studies for immediate-release solid oral dosage forms for a Class 1 drug substance based on the Biopharmaceutics Classification System (highly soluble and highly permeable) and for a rapidly dissolving product. ... 

Where an unusual excipient is chosen, or where an established excipient is chosen for a dosage form that results in its administration by a novel route of administration, then additional data will need to form part of the application. In effect, a novel excipient will need to be supported by data similar to those required for a new drug, with full supporting data including composition, function, and safety. Novel excipients include the components of the matrix in prolonged release products, new propellants, and new permeability enhancers. The exception to this need for extensive supporting data would be for a material already approved for food use and administered by the oral route or a material already approved for cosmetic use with a topical route of administration. In all cases the quality of the excipients has to be described adequately and shown to be satisfactory (which will depend on its role). 

Although, the pH-partition hypothesis has not been found to be universally applicable, it has resulted in the recognition of the important contribution of GI pH to permeability and to the dissolution rate of solid dosage forms. This theory does not consider the solubility of the drug, which is a critical physicochemical parameter in the oral absorption process. Dressman et al. [34] developed an absorption potential concept that takes the two parameters into account. The absorption potential is defined as... 

---