Pluronic ® F127 gel formulations of Deslorelin and GnRH reduce drug degradation and sustain drug release and effect in cattle

• Published in: Journal of controlled release 2002-12, Vol.85 (1), p.51-59
• Main Authors: Wenzel, James G.W, Balaji, K.S.Sree, Koushik, Kavitha, Navarre, Christine, Duran, Sue H, Rahe, C.Hardin, Kompella, Uday.B
• Format: Article
• Language: English
• Subjects: Animals; Cattle; Chemistry, Pharmaceutical; Delayed-Action Preparations - chemistry; Delayed-Action Preparations - pharmacokinetics; Deslorelin; Gels; GnRH; Gonadotropin-Releasing Hormone - blood; Gonadotropin-Releasing Hormone - chemistry; Gonadotropin-Releasing Hormone - pharmacokinetics; Pluronic gel; Poloxamer - chemistry; Poloxamer - pharmacokinetics; Sustained release; Triptorelin Pamoate - analogs & derivatives; Triptorelin Pamoate - blood; Triptorelin Pamoate - chemistry; Triptorelin Pamoate - pharmacokinetics
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/S0168-3659(02)00271-7

The objective of this study was to compare the effectiveness of intramuscular sustained release Pluronic ® F127 (PF127) gel formulations of deslorelin, a potent GnRH agonist, and GnRH to their solution formulations in inducing the release of luteinizing hormone and formation of luteal tissue in cattle. Injectable gel formulations of deslorelin and GnRH were prepared using Pluronic ® F127 (25%, w/w), a block copolymer. PF127 gels sustained the in vitro release of deslorelin as well as GnRH at similar rates and reduced drug degradation in muscle tissue when compared to the solution formulations. Deslorelin, as well as GnRH, elicited desirable elevations in plasma LH and progesterone concentrations in vivo. When compared to the solution formulations, the gel formulations of both drugs induced a broader peak of LH. Also, the peak LH levels were lower and the peak times were delayed with the gel formulations compared to the solution formulations. While the solution dosage form of deslorelin and GnRH elicited similar responses, the PF127 gel formulation of deslorelin induced peak LH levels at an earlier time (3 h for deslorelin versus 5.25 h for GnRH). The results indicate that, deslorelin exerts a pharmacological effect in cattle. The LH response to deslorelin as well as GnRH can be altered by controlling the input or the release rate of the drug. PF127 gel formulations can sustain peptide release and reduce peptide degradation.