Dynamic light scattering (DLS) was used to study the droplet size and the droplet interaction of o/w microemulsions (MEs) consisting of oils, a blend of a high and a low hydrophilic-lipophilic balance (HLB) surfactant, and a hydrophilic phase (propylene glycol/water). Like many MEs, these systems could not be diluted to infinite dilution without phase separation. Consequently, to allow a meaningful calculation of droplet diameter from data obtained from DLS, it is necessary to correct scattering measurements in high concentration regions for the nonideality arising from interparticle interaction. Scattering data were corrected for interparticle interaction using a suitable interaction model proposed for our systems. From the total interparticle interaction energy, coagulation time was calculated. The ratio between rapid and slow coagulation was of the order of 10(100), which is consistent with the observed stability of the MEs studied.

A sensitive and selective method for the quantification of mycophenolate mofetil and its active metabolite mycophenolic acid in different human skin layers after dermal administration is presented. The skin layers were separated after in vitro penetration experiments and a methanolic extraction was performed. Positive ion electrospray HPLC-MS in selected ion monitoring mode was used to quantify the substances after isocratic separation by a C18 analytical column. The minimum detectable concentrations were 850 pg/ml for MMF and 1 ng/ml for MPA. The peak areas depended linearly on the concentration of both drugs over the range of 25-1,000 ng/ml (r2 > or = 0.996) with accuracy < or =9.8% and precision < or = 13.2%. Total imprecision at quantification limits was 15.2% at 10 ng/ml and 16.3% at 1,500 ng/ml for MMF and 15.1% at 21.0 ng/ml and 17.5% at 1,300 ng/ml for MPA. This HPLC-MS method will be applicable to the profiling of MMF amounts in skin and its conversion to MPA after application of different formulations.

Mycophenolate mofetil, the morpholinoethylester of mycophenolic acid, is an immunosuppressant used in combination with ciclosporin (cyclosporin) and corticosteroids to prevent organ rejection after heart and kidney transplantations. The drug seems also to be effective in dermal diseases after systemic administration. However, up to date mycophenolate mofetil can be only systemically administered and this is associated with several side effects such as nausea, leucopenia, sepsis, and diarrhoea. The aim of this study was to develop a topical formulation containing mycophenolate mofetil and to investigate in-vitro release and penetration into human skin ex-vivo. HPLC was applied to quantify mycophenolate mofetil after release studies from semisolid formulations using a dodecanol-collodion membrane as a lipophilic acceptor. Penetration studies with an amphiphilic cream using excised human breast skin were carried out in Franz-type diffusion cells. Mycophenolate mofetil and its active metabolite mycophenolic acid were detected by HPLC-MS after microsectioning in different skin layers. In this study the penetration of mycophenolate mofetil from an amphiphilic cream into excised human skin was shown. Additionally, the enzymatic hydrolysis of penetrated mycophenolate mofetil into mycophenolic acid was proven even under ex-vivo conditions. In-vivo a higher extent of metabolism of mycophenolate mofetil to mycophenolic acid would be expected because of the complete enzyme activity. This topical formulation might be a promising alternative to the usual systemic administration of mycophenolate mofetil in the treatment of skin diseases such as psoriasis.