BIODEGRADABLE MICROSPHERES AS A DELIVERY SYSTEM FOR RISMORELIN PORCINE, A PORCINE-GROWTH-HORMONE-RELEASING-HORMONE

Biodegradable controlled release microspheres containing rismorelin po rcine, a potent analog of growth-hormone-releasing-hormone (GHRH), and poly(D,L-lactide-co-glycolide) were prepared by a modified solvent ev aporation technique. Release rates of rismorelin porcine were characte rized in vitro by use of a cell perifusion system and evaluated in viv o 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 th e high water solubility of rismorelin porcine, a modified solvent evap oration procedure was used to prepare poly(D,L-lactide-co-glycolide) m icrospheres. The aqueous phase was modified by the inclusion of phosph ate salts to prevent rismorelin porcine solubilization during microsph ere formation. Rismorelin porcine loading levels evaluated were 5% w/w , 10% w/w, and 25% w/w. Rismorelin porcine loading level determined ra te and total amount of peptide released from microspheres in vitro and in vivo. The biological efficacy of the rismorelin porcine microspher es was determined in finishing swine by urinary urea nitrogen (UUN) de pression as well as by serum blood urea nitrogen (BUN). Depression of both UUN and BUN was noted upon subcutaneous administration of rismore lin porcine microspheres. The nature of the injection vehicle used to suspend the microspheres for injection influenced in vivo release of r ismorelin porcine. Physical site of injection of microspheres did not influence release profile in swine. In vivo release of rismorelin porc ine from microspheres ceased after nine to twelve days in all studies.