Biopharmaceutical classification of drugs using intrinsic dissolution rate (IDR) and rat intestinal permeability

Abstract

The solubility and dissolution rate of active ingredients are of major importance in preformulation studies of pharmaceutical dosage forms. In the present study, passively absorbed drugs are classified based on their intrinsic dissolution rate (IDR) and their intestinal permeabilities. IDR was determined by measuring the dissolution of a non-disintegrating disk of drug, and effective intestinal permeability of tested drugs in rat jejunum was determined using single perfusion technique. The obtained intrinsic dissolution rate values were in the range of 0.035–56.8 mg/min/cm 2 for tested drugs. The minimum and maximum intestinal permeabilities in rat intestine were determined to be 1.6 × 10 −5 and 2 × 10 −4 cm/s, respectively. Four classes of drugs were defined: Category I: P eff,rat > 5 × 10 −5 (cm/s) or P eff,human > 4.7 × 10 −5 (cm/s), IDR > 1(mg/min/cm 2), Category II: P eff,rat > 5 × 10 −5 (cm/s) or P eff,human > 4.7 × 10 −5 (cm/s), IDR < 1(mg/min/cm 2), Category III: P eff,rat < 5 × 10 −5 (cm/s) or P eff,human < 4.7 × 10 −5 (cm/s), IDR > 1 (mg/min/cm 2) and Category IV: P eff,rat < 5 × 10 −5 (cm/s) or P eff,human < 4.7 × 10 −5 (cm/s), IDR < 1(mg/min/cm 2). According to the results obtained and proposed classification of drugs, it is concluded that drugs could be categorized correctly based on their IDR and intestinal permeability values.