IN-VITRO EVALUATION OF POLY(D,L-LACTIDE-CO-GLYCOLIDE) POLYMER-BASED IMPLANTS CONTAINING THE ALPHA-MELANOCYTE-STIMULATING HORMONE ANALOG, MELANOTAN-I

The release of the melanotropic peptide, Melanotan-I (MT-I), from biod egradable implants of poly(D,L lactide-co-glycolide) (PLGA) copolymer was studied. The implants were prepared by a melt-extrusion method. Th e in vitro release of MT-I exhibited a triphasic profile with an initi al rapid release followed by a secondary phase of slow release, then a tertiary phase of rapid release due to erosion of the polymer. The in itial rapid release observed with PLGA (50:50 molar ratio of lactic/gl ycolic acid) polymers was less than 5% of the drug load and the tertia ry phase commenced after about 3 weeks. The factors controlling the dr ug release are degradation and erosion of the polymer which may, in tu rn, be controlled by the physical properties of the polymer such as mo lecular weight and viscosity. The influence of viscosity (0.2-1.08 dl/ g) of the polymer, on the release kinetics of MT-I were analyzed and t he polymer having a viscosity of 0.6 dl/g was selected for preparing a 1-month implant system. Molecular weight distribution analysis indica ted a biphasic rate of molecular weight reduction and within 12 days, the molecular weight had decreased to 50% of the initial value. The re lease rate was examined at different drug loading levels and in the pr esence of some hydrophilic additives. The effect of gamma radiation on the release kinetics of the peptide was analyzed to determine the opt imal radiation sterilization dose for the PLGA implants. There was no significant difference in the total duration of MT-I release between t he implants exposed to no radiation and the 2.5 Mrad dose selected.