PURPOSE: To classify the dissolution and diffusion rate-limited drugs and establish quantitative relationships between absorption and molecular descriptors. METHODS: Absorption consists of kinetic transit processes in which dissolution, diffusion, or perfusion processes can become the rate-limited step. The absorption data of 238 drugs have been classified into either dissolution or diffusion rate-limited based on an equilibrium method developed from solubility, dose, and percentage of absorption. A nonlinear absorption model derived from first-order kinetics has been developed to identify the relationship between percentage of drug absorption and molecular descriptors. RESULTS: Regression analysis was performed between percentage of absorption and molecular descriptors. The descriptors used were ClogP, molecular polar surface area, the number of hydrogen-bonding acceptors and donors, and Abraham descriptors. Good relationships were found between absorption and Abraham descriptors or ClogP. CONCLUSIONS: The absorption models can predict the following three BCS (Biopharmaceutics Classification Scheme) classes of compounds: class I, high solubility and high permeability; class III, high solubility and low permeability; class IV, low solubility and low permeability. The absorption models overpredict the absorption of class II, low solubility and high permeability compounds because dissolution is the rate-limited step of absorption.
PURPOSE: To classify the dissolution and diffusion rate-limited drugs and establish quantitative relationships between absorption and molecular descriptors. METHODS: Absorption consists of kinetic transit processes in which dissolution, diffusion, or perfusion processes can become the rate-limited step. The absorption data of 238 drugs have been classified into either dissolution or diffusion rate-limited based on an equilibrium method developed from solubility, dose, and percentage of absorption. A nonlinear absorption model derived from first-order kinetics has been developed to identify the relationship between percentage of drug absorption and molecular descriptors. RESULTS: Regression analysis was performed between percentage of absorption and molecular descriptors. The descriptors used were ClogP, molecular polar surface area, the number of hydrogen-bonding acceptors and donors, and Abraham descriptors. Good relationships were found between absorption and Abraham descriptors or ClogP. CONCLUSIONS: The absorption models can predict the following three BCS (Biopharmaceutics Classification Scheme) classes of compounds: class I, high solubility and high permeability; class III, high solubility and low permeability; class IV, low solubility and low permeability. The absorption models overpredict the absorption of class II, low solubility and high permeability compounds because dissolution is the rate-limited step of absorption.
Authors: Y H Zhao; J Le; M H Abraham; A Hersey; P J Eddershaw; C N Luscombe; D Butina; G Beck; B Sherborne; I Cooper; J A Platts; D Boutina Journal: J Pharm Sci Date: 2001-06 Impact factor: 3.534
Authors: Ashraf A Aly; Essmat M El-Sheref; Momtaz E M Bakheet; Mai A E Mourad; Stefan Bräse; Mahmoud A A Ibrahim; Martin Nieger; Boyan K Garvalov; Kevin N Dalby; Tamer S Kaoud Journal: Bioorg Chem Date: 2018-10-23 Impact factor: 5.275
Authors: I-Jen Chen; Rajneesh Taneja; Daxu Yin; Paul R Seo; David Young; Alexander D MacKerell; James E Polli Journal: Mol Pharm Date: 2006 Nov-Dec Impact factor: 4.939