MATHEMATICAL ASSESSMENT OF DIFFERENT PENETRATION MECHANISMS FROM VEHICLES WITH PROPYLENE-GLYCOL

A compartmental model describing the penetration of drugs into lipophi lic membranes is developed. The model is derived to simulate the role of dissolution and two different penetration mechanisms, i.e. simple p enetration and cotransport, for the penetration from suspension-type v ehicles containing propylene glycol (PG). Simple penetration is referr ed to the drug transport based on the gradient of the chemical potenti als of the drug in the formulation and the acceptor. Cotransport is dr ug penetration together with the penetrating cosolvent (PG). Using exp erimental data for the penetration of the glucocorticoids betamethason e valerate (BMV) and hydrocortisone (HC) from PG/water formulations in to dodecanol (DD) membranes as acceptor, the time-dependent mass alter ations in all compartments are assessed by means of the model equation s. Thus, the rate-limiting step of the penetration process can be dete rmined. Covering substances with different solubilities in PG, the stu dy indicates that the fraction of drug penetrating by cotransport incr eases as the solubility in PG increases. Furthermore, a higher Po cont ent in the vehicle leads to a markedly higher importance of the cotran sport pathway. (C) 1997 Elsevier Science B.V.