LAUSR

The feasibility of hot-melt processing of a peptide active pharmaceutical ingredient was assessed by developing a non-biodegradable poly(ethylene-vinyl acetate) (33% VA) implant loaded with 20% (w/w) buserelin acetate. No significant quantities of buserelin acetate-related degradation products were formed during this hot-melt preparation. Cross-sectional implant characterization by Raman microscopy showed the solid dispersion distribution of the buserelin acetate powder in the polymeric matrix. The in vitro buserelin acetate release from the implant was assessed in PBS and found to be diffusion-controlled, releasing on average 5 µg buserelin acetate daily after an initial burst release. The stability of buserelin acetate in the polymeric matrix was evaluated for three months under ICH stability conditions (5°C, 25°C/60% R.H. and 40°C/75% R.H.). Given the consistent buserelin acetate assay values, combined with the absence of degradation products, chemical peptide stability was demonstrated. Moreover, stable in vitro release profiles were obtained in the stability study, demonstrating the functional stability of the peptide implant. These results indicate the feasibility of preparing non-biodegradable peptide-loaded implants using the hot-melt production method and may act as a proof of principle concept for further innovation in peptide medicinal formulations.