The utility of rat jejunal permeability for biopharmaceutics classification system

Abstract

Purpose: The biopharmaceutical classification system has been developed to provide a scientific approach for classifying drug compounds based on their dose/solubility ratio and human intestinal permeability. Therefore in this study a new classification is presented, which is based on a correlation between rat and human intestinal permeability values. Methods: In situ technique in rat jejunum was used to determine the effective intestinal permeability of tested drugs. Then three dimensionless parameters—dose number, absorption number, and dissolution number (D_o, A_n, and D_n)—were calculated for each drug. Results: Four classes of drugs were defined, that is, class I, D₀ < 0.5, P_eff(rat) > 5.09 × 10⁻⁵ cm/s; class II, D_o > 1, P_eff(rat) > 5.09 × 10⁻⁵ cm/s; class III, D₀ < 0.5, P_eff(rat) < 4.2 × 10⁻⁵ cm/s; and class IV, D_o > 1, P_eff(rat) < 4.2 × 10⁻⁵ cm/s. A region of borderline drugs (0.5 < D_o < 1, 4.2 × 10⁻⁵ < P_eff(rat) < 5.09 × 10⁻⁵ cm/s) was also defined. Conclusion: According to obtained results and proposed classification for drugs, it is concluded that drugs could be categorized correctly based on dose number and their intestinal permeability values in rat model using single-pass intestinal perfusion technique. This classification enables us to remark defined characteristics for intestinal absorption of all four classes using suitable cutoff points for both dose number and rat effective intestinal permeability values.

Keywords:

• Biopharmaceutics classification
• dissolution
• permeability
• rat jejunal permeability
• solubility
• single-pass intestinal perfusion