Polyglycerol fatty acid ester surfactant-based microemulsions for targeted delivery of ceramide AP into the stratum corneum: formulation, characterisation, in vitro release and penetration investigation.
Ceramide AP (CER [AP]) is an integral component of the stratum corneum (SC) lipid matrix and is capable of forming tough and super stable lamellae. It may help to restore the barrier function in aged and affected skin. However, its effectiveness from conventional dosage forms is limited due to its poor solubility and penetration into the SC. Therefore, stable polyglycerol fatty acid ester surfactant (SAA)-based CER [AP] microemulsions (MEs) were formulated and characterised to enhance its solubilisation and penetration into the SC. TEGO® CARE PL 4 (TCPL4: polyglycerol-4-laurate), isopropyl palmitate (IPP) and water-1, 2 pentandiol (PeG) were used as amphiphilic, oily and hydrophilic components, respectively. The effects of HYDRIOL® PGMO.4 (HPGMO4: polyglyceryl-4-oleate) as a co-surfactant (co-SAA) and linoleic acid (Lin A) as part of the oil component on the stability and characteristics of the MEs were investigated. EPR results were used for the first time to reveal MEs nanostructures. The release and penetration behaviour of the MEs was assessed in vitro by using a multi-layer membrane model. The results obtained showed that HPGMO4 and Lin A increased stability and expanded the ME region considerably. The formulations were stable for 10 to >24 months. Dynamic light scattering (DLS) results showed that the droplets were bigger and asymmetric, which might be helpful to localise the CER into the upper layers of the epidermis. Release and penetration from the MEs was superior as compared to the hydrophilic cream (DAB). The rate and extent of CER [AP] released and penetrated from O/W MEs was better than W/O MEs.
Department of Pharmaceutical Technology and Biopharmaceutics, Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
Fitsum F
FF
Sahle
Hendrik
H
Metz
Johannes
J
Wohlrab
Reinhard H H
RH
Neubert
D002518:Ceramides / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D004355:Drug Stability; D004356:Drug Storage; D004655:Emulsions; D005227:Fatty Acids / Q000737:chemistry*; D005990:Glycerol / Q000737:chemistry; D008027:Light; D008954:Models, Biological; D049329:Nanostructures; D010316:Particle Size; D010539:Permeability; D011108:Polymers / Q000737:chemistry; D012542:Scattering, Radiation; D012867:Skin; D012869:Skin Absorption; D013501:Surface-Active Agents / Q000737:chemistry*; D013997:Time Factors
D002518:Ceramides; D004655:Emulsions; D005227:Fatty Acids; D011108:Polymers; D013501:Surface-Active Agents; C043941:polyglycerol; D005990:Glycerol