Simultaneous release and ADME processes of poorly water-soluble drugs: mathematical modeling.
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.
Grassi
Gabriele
G
Department of Life Sciences, University of Trieste, Via Giorgieri, 1, I-34127, Department of Medical, Technological and Translational Sciences, University Hospital of Cattinara, Trieste, Italy.
Hasa
Dritan
D
Voinovich
Dario
D
Perissutti
Beatrice
B
Dapas
Barbara
B
Farra
Rossella
R
Franceschinis
Erica
E
Grassi
Mario
M
D000284:Administration, Oral; D000328:Adult; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D055641:Mathematical Concepts; D008875:Middle Aged; D008954:Models, Biological; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D010599:Pharmacokinetics; D012995:Solubility; D014748:Vinca Alkaloids / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D014867:Water
D003692:Delayed-Action Preparations; D014748:Vinca Alkaloids; D014867:Water; C013983:vinpocetine