Estimating the Fraction Dose Absorbed from Suspensions of Poorly Soluble Compounds in Humans: A Mathematical Model

Abstract

A microscopic mass balance approach has been developed to predict the fraction dose absorbed of suspensions of poorly soluble compounds. The mathematical model includes four fundamental di-mensionless parameters to estimate the fraction dose absorbed: initial saturation ( Is ), absorption number ( An ), dose number ( Do ), and dissolution number ( Dn ). The fraction dose absorbed ( F ) increases with increasing Is , An , and Dn and with decreasing Do . At higher Dn and lower Do , the fraction dose absorbed reaches the maximal F , which depends only on An . The dissolution number limit on F can appear at both lower Do and lower Dn . Likewise, at higher Do and Dn , the fraction dose absorbed reaches a Do limit. Initial saturation makes a significant difference in F at lower Do and Dn . It is shown that the extent of drug absorption is expected to be highly variable when Dn and Do are approximately one. Furthermore, by calculating these dimensionless groups for a given compound, a formulation scientist can estimate not only the extent of drug absorption but also the effect, if any, of particle size reduction on the extent of drug absorption.