AN ATTEMPT TO CLARIFY THE MECHANISM OF THE PENETRATION ENHANCING EFFECTS OF LIPOPHILIC VEHICLES WITH DIFFERENTIAL SCANNING CALORIMETRY (DSC)

In a previous in-vivo skin penetration study, it was observed that cer tain lipophilic liquid vehicles enhanced drug penetration, whilst othe rs did not. To clarify the mechanism of skin penetration enhancement, isolated sheets of human stratum corneum were measured by differential scanning calorimetry (DSC), either untreated or after pretreatment wi th various lipophilic liquids (highly purified light mineral oil, isop ropyl myristate, caprylic/capric acid triglycerides containing 5% phos pholipids, dibutyl adipate, dimethicone 100, cetearyl iso-octanoate, c aprylic/capric acid triglycerides), commonly used in ointment bases. A ll samples were analysed over a heating range of at least - 10-130 deg rees C. All DSC curves were evaluated with regard to the phase-transit ion enthalpies (peak areas) and peak maximum temperatures of the lipid -phase transitions at ca 75 and 85 degrees C. With the exception of di methicone 100, cetearyl iso-octanoate and caprylic/capric acid triglyc erides, all vehicles showed characteristic alterations of the phase-tr ansition temperatures and enthalpies of the stratum corneum lipids. Mi neral oil and isopropyl myristate caused a reduction of the enthalpy a nd a decrease of the phase-transition temperatures. These two vehicles are thought to fluidize the lamellar-gel phase of the stratum corneum lipids, and possibly partially dissolve the lipids. Dibutyl adipate a nd caprylic/capric acid triglycerides containing 5% phospholipids decr eased the phase-transition enthalpy only, probably due to dissolution or extraction of the stratum corneum lipids. These DSC results provide an explanation for the in-vivo penetration-enhancing effects observed previously.