Biodegradable microspheres as a delivery system for rismorelin porcine, a porcine-growth-hormone-releasing-hormone

Biodegradable controlled release microspheres containing rismorelin porcine, a potent analog of growth-hormone-releasing-hormone (GHRH), and poly(D,L-lactide-co-glycolide) were prepared by a modified solvent evaporation technique. Release rates of rismorelin porcine were characterized in vitro by use of a cell perifusion system and evaluated in vivo in pigs. Rismorelin porcine is 4-methylhippuroyl (1) porcine GHRH (2-76)-OH, which is a potent analog of a natural porcine GHRH. Due to the high water solubility of rismorelin porcine, a modified solvent evaporation procedure was used to prepare poly(D,L-lactide-co-glycolide) microspheres. The aqueous phase was modified by the inclusion of phosphate salts to prevent rismorelin porcine solubilization during microsphere formation. Rismorelin porcine loading levels evaluated were 5% w/w, 10% w/w, and 25% w/w. Rismorelin porcine loading level determined rate and total amount of peptide released from microspheres in vitro and in vivo. The biological efficacy of the rismorelin porcine microspheres was determined in finishing swine by urinary urea nitrogen (UUN) depression as well as by serum blood urea nitrogen (BUN). Depression of both UUN and BUN was noted upon subcutaneous administration of rismorelin porcine microspheres. The nature of the injection vehicle used to suspend the microspheres for injection influenced in vivo release of rismorelin porcine. Physical site of injection of microspheres did not influence release profile in swine. In vivo release of rismorelin porcine from microspheres ceased after nine to twelve days in all studies.