Simultaneous release and ADME processes of poorly water-soluble drugs: mathematical modeling

Mol Pharm. 2010 Oct 4;7(5):1488-97. doi: 10.1021/mp1001334. Epub 2010 Aug 3.

Abstract

The importance of studying oral drug absorption is well recognized by both research facilities/institutions and the pharmaceutical industry. The use of mathematical models can represent a very profitable and indispensable tool to understand oral drug absorption. Indeed, mathematical models can verify the correctness of the mechanisms proposed to describe drug release, absorption, distribution and elimination thus reducing the number of expensive and time-consuming experiments. In this paper we develop a mathematical approach able to model both the polymeric particle mediated delivery and the gastrointestinal absorption-metabolism-excretion (ADME) of a given drug. As a model drug a poorly water-soluble drug (vinpocetine) in both the amorphous and nanocrystalline state is considered. The delivery system is obtained by drug cogrinding with a polymer (cross-linked polyvinilpyrrolidone). As the proposed mathematical model can properly fit the in vivo data on the basis of information obtained in vitro, it represents a powerful theoretical tool connecting in vitro and in vivo behavior.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Chemistry, Pharmaceutical
  • Crystallization
  • Delayed-Action Preparations
  • Drug Delivery Systems
  • Humans
  • Intestinal Absorption*
  • Male
  • Mathematical Concepts
  • Middle Aged
  • Models, Biological*
  • Nanoparticles / administration & dosage
  • Nanoparticles / chemistry
  • Pharmacokinetics*
  • Solubility
  • Vinca Alkaloids / administration & dosage
  • Vinca Alkaloids / chemistry
  • Vinca Alkaloids / pharmacokinetics
  • Water

Substances

  • Delayed-Action Preparations
  • Vinca Alkaloids
  • Water
  • vinpocetine