Percutaneous delivery of α-melanocyte-stimulating hormone for the treatment of imiquimod-induced psoriasis.

PURPOSE: α-Melanocyte-stimulating hormone (α-MSH) is an endogenous peptide hormone with anti-inflammatory responses. We developed topical formulation(s) of α-MSH to reduce psoriasis-related inflammation. METHODS: Transcutol (TC) and n-methyl 2-pyrrolidone (NMP) were used to formulate a gel for α-MSH. Skin permeation and dermal microdialysis of the solution and optimized gel were performed. The inflammatory response of α-MSH gel was investigated in imiquimod-induced psoriasis mouse model. Histology and immunohistochemistry were then performed on treated skin. RESULTS: Solution comprising 50%w/w TC and 10%w/w NMP showed higher (p < 0.05) skin retention (0.27 ± 0.024 µg of α-MSH/mg of skin) than solutions containing either 50% w/w TC or 10% w/w NMP at 24 h. Dispersion of α-MSH in Carbopol Ultrez 10 produced a uniform dispersion. α-MSH gel showed pseudoplastic flow with thixotropic behavior. Dermal microdialysis results suggested that skin permeation of gel after 5 h was 1.9-folds higher than the solution. Further, gel-treated psoriatic-like plaque skin sections showed significant (p < 0.05) decrease in the expression of a melanocortin receptor, in the psoriasis area and severity index score and transepidermal water loss compared to the solution. CONCLUSION: TC, NMP and Carbopol Ultrez 10 form a stable gel with improved skin permeation of α-MSH for a reduction in psoriasis-associated inflammation.

The USP Performance Verification Test, Part I: USP Lot P Prednisone Tablets: quality attributes and experimental variables contributing to dissolution variance.

PURPOSE: Beyond instrumental qualification, proficiency testing is not usually a prerequisite for many analytical procedures, given reliance on a manufacturer's assay validation coupled with regulatory review and inspection. Given the special features of the dissolution procedure, proficiency testing was put in place initially by pharmaceutical manufacturers and carried on by USP. Proficiency testing is designed to help ensure that execution of a dissolution procedure for solid oral dosage forms adequately supports administrative and legal decisions so that measurements made at different times, by different analysts, or with different methods can be confidently compared. USP has applied metrological principles to aid practitioners in carrying out the dissolution procedure alone and in collaborative studies to facilitate understanding potential sources of variability. MATERIALS AND METHODS: The present study aimed to identify key dissolution variables associated with USP Lot P Prednisone Tablets in conjunction with the USP Performance Verification Test (PVT). Using five dissolution test assemblies from different manufacturers, at least four of six analysts determined percents prednisone dissolved on dissolution Apparatus 1 (basket) and Apparatus 2 (paddle) on each assembly. Six replicate experiments were performed on each analyst-assembly combination with a set of six to eight tablets in each experiment. RESULTS AND CONCLUSIONS: Statistical analysis demonstrated that dissolution test assemblies were the largest factor contributing to dissolution variability. Inherent tablet variability was low, and USP Lot P Prednisone Tablets did not contribute importantly to dissolution variability. Contributions from analyst and analytical procedure also were estimated to be low.