Synergetic effects of isopropyl alcohol (IPA) and isopropyl myristate (IPM) on the permeation of betamethasone-17-valerate from semisolid Pharmacopoeia bases

Abstract

Betamethasone-17-valerate (BM-17-V) is a corticosteroid commonly administered in semisolid preparations for cutaneous use. In this study, an ointment and a cream from the German Pharmacopoeia, i.e. wool fat alcohol ointment (WS) and basis cream DAC were loaded separately with BM-17-V. Two conventional penetration enhancers, namely isopropyl alcohol (IPA) and isopropyl myristate (IPM) as sole additives, as well as a mixture of both, IPA-IPM 1:1 (w/w) were also incorporated into the different semisolid formulations and in vitro permeation experiments of BM- 17-V were carried out in Franz diffusion cells using excised human stratum corneum (SC). The effect of the additives on the thermal behavior of the SC lipid matrix was evaluated by differential scanning calorimetry (DSC). The saturation concentrations of BM-17-V within the formulations were estimated based on microscopical characterization. BM-17-V is transformed into its hydrolization product, betamethasone (BM), during the permeation experiments by the effect of the SC using the BM-21-V pathway. Furthermore the microstructure of the lipids and protein complexes located at the membrane of the corneocytes was altered by the use of the enhancers. The combination of IPA and IPM resulted in a synergetic enhancement of the BM flux. The BM permeation was augmented by approximately 12 times when a combination of IPA-IPM 1:1 (w/w) was used in wool fat alcohol ointment.