Role of isopropyl myristate, isopropyl alcohol and a combination of both in hydrocortisone permeation across the human stratum corneum.
The influence of isopropyl myristate (IPM), isopropyl alcohol (IPA) and a combination of both was studied in view of hydrocortisone (HC) permeation across the human stratum corneum (SC). IPM, IPA and their combination were incorporated into water-containing hydrophilic ointment (WHS), and the resulting effects on HC permeation and on HC accumulation in human SC were investigated as well as the influence of these substances on the microstructure of the SC. Differential scanning calorimetry as well as wide- and small-angle X-ray diffraction show that IPM incorporation into SC results in densely packed bilayer lipids and a loss of order of the corneocyte-bonded lipids. Both effects result in a decreased diffusion coefficient of HC in SC and thus in a decreased permeation rate compared to that of HC from WHS. On the other hand, IPA fluidizes and disrupts the bilayer structure of the intercellular lipids. These effects, concomitant with an increased amount of dissolved HC within the ointment, increase the permeation rate of HC across SC. The combination of both ingredients effects a stronger fluidization and disruption of intercellular lipids than with IPA alone. Therefore, the permeation rate of HC across SC is higher than with IPA alone. Consequently, the IPM and IPA combination acts synergistically on the microstructure of SC.
Brinkmann
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Institut für Pharmazeutische Technologie, Technische Universität Carolo-Wilhelmina zu Braunschweig, Braunschweig, Germany.
Müller-Goymann
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CC
D019840:2-Propanol / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D002152:Calorimetry, Differential Scanning; D002851:Chromatography, High Pressure Liquid; D004338:Drug Combinations; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000737:chemistry / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D008875:Middle Aged; D009226:Myristates / Q000494:pharmacology*; D009824:Ointments; D010539:Permeability / Q000187:drug effects; D012869:Skin Absorption / Q000187:drug effects*; D012997:Solvents / Q000494:pharmacology*; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature; D014961:X-Ray Diffraction
D000893:Anti-Inflammatory Agents; D004338:Drug Combinations; D009226:Myristates; D009824:Ointments; D012997:Solvents; C008205:isopropyl myristate; D019840:2-Propanol; D006854:Hydrocortisone