Lecithin-Based Microemulsions for Targeted Delivery of Ceramide AP into the Stratum Corneum: Formulation, Characterizations, and In Vitro Release and Penetration Studies

• Published in: Pharmaceutical research Vol. 30; no. 2; pp. 538 - 551
• Main Authors: Sahle, Fitsum F., Metz, Hendrik, Wohlrab, Johannes, Neubert, Reinhard H. H.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.02.2013; Springer; Springer Nature B.V
• Subjects: Biochemistry; Biological and medical sciences; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Ceramides - administration & dosage; Ceramides - pharmacokinetics; Drug Delivery Systems; Electric Conductivity; Emulsions - chemistry; Epidermis - metabolism; General pharmacology; Humans; Lecithins - chemistry; Lipids; Medical Law; Medical sciences; Membranes, Artificial; Microemulsions; Particle Size; Pharmaceutical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pharmacy; Refractometry; Research Paper; Transdermal medication; Viscosity; stratum corneum; microemulsions; lecithin; release and penetration; ceramide [AP]; Stratum corneum; Pharmaceutical technology; Targeted therapy; Sphingolipid; In vitro; Characterization; Penetration; Formulation; Ceramide; Phosphatidylcholine; Microemulsion; Release
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-012-0899-x

ABSTRACT Purpose To improve the solubility and penetration of Ceramide AP (CER [AP]) into the stratum corneum that potentially restores the barrier function of aged and affected skin. Methods CER [AP] microemulsions (MEs) were formulated using lecithin, Miglyol® 812 (miglyol) and water-1,2 pentandiol (PeG) mixture as amphiphilic, oily and hydrophilic components, respectively. The nanostructure of the MEs was revealed using electrical conductivity, differential scanning calorimeter (DSC) and electron paramagnetic resonance (EPR) techniques. Photon correlation spectroscopy (PCS) was used to measure the sizes and shape of ME droplets. The release and penetration of the CER into the stratum corneum was investigated in vitro using a multi-layer membrane model. Results The MEs exhibited excellent thermodynamic stability (>2 years) and loading capacity (0.5% CER [AP]). The pseudo-ternary phase diagrams of the MEs were obtained and PCS results showed that the droplets are spherical in shape and bigger in size. In vitro investigations showed that the MEs exhibited excellent rate and extent of release and penetration. Conclusions Stable lecithin-based CER [AP] MEs that significantly enhance the solubility and penetration of CER [AP] into the stratum corneum were developed. The MEs also have better properties than the previously reported polyglycerol fatty acid surfactant-based CER [AP] MEs.