Mathematical assessment of different penetration mechanisms from vehicles with propylene glycol

A compartmental model describing the penetration of drugs into lipophilic membranes is developed. The model is derived to simulate the role of dissolution and two different penetration mechanisms, i.e. simple penetration and cotransport, for the penetration from suspension-type vehicles containing propylene glycol (PG). Simple penetration is referred to the drug transport based on the gradient of the chemical potentials of the drug in the formulation and the acceptor. Cotransport is drug penetration together with the penetrating cosolvent (PG). Using experimental data for the penetration of the glucocorticoids betamethasone valerate (BMV) and hydrocortisone (HC) from PG/water formulations into dodecanol (DD) membranes as acceptor, the time-dependent mass alterations in all compartments are assessed by means of the model equations. Thus, the rate-limiting step of the penetration process can be determined. Covering substances with different solubilities in PG, the study indicates that the fraction of drug penetrating by cotransport increases as the solubility in PG increases. Furthermore, a higher Po content in the vehicle leads to a markedly higher importance of the cotransport pathway. (C) 1997 Elsevier Science B.V.