Development and optimization of in-situ forming microparticles for long term controlled delivery of deslorelin acetate

Deepak Kapoor ,Om Prakash Katare ,Hemlata Kaurav ,Sanju Dhawan

doi:10.7324/japs.2018.8110

Abstract

Deslorelin is a nonapeptide analogue of the natural gonadotropin releasing hormone or luteinizing hormone releasing hormone used in the treatment of prostate cancer, endometriosis and uterine fibroids. In-situ forming microparticles were developed for deslorelin using smart, biodegradable polymer i.e. PLGA. Different formulations were designed, prepared and evaluated by employing response surface, I-optimal design. To determine the optimized formulation, numerical and graphical optimization techniques were employed. The resulting optimized formulation was evaluated for other physicochemical parameters viz., rheology, particle size distribution, surface morphology of the particles, peptide conformation stability in the formulation and stability study at different environmental conditions. It was concluded that the optimized deslorelin acetate ISFM formulation effectively extended the peptide release for 30 days while maintaining its conformational stability during the period of study. The optimized ISFM formulation was found to be stable at 5°C ± 2°C and 25°C ± 2°C during 6 months stability studies.

Highlights

Unlike conventional small molecules, therapeutic proteins are difficult to be administered orally because they are liable to degradation by the harsh gastric environment, hepatic metabolism and short half-lives thereby necessitating frequent administration of high doses by parenteral route (Cleland et al, 2001; Fu et al, 2000; Robinson and Talmadge, 2002)
Deslorelin is a nonapeptide analogue of the natural gonadotropin releasing hormone or luteinizing hormone releasing hormone used to treat prostate cancer, endometriosis and uterine fibroids
It was concluded that the optimized deslorelin acetate in-situ forming microparticles” (ISFM) formulation effectively extended the peptide release for 30 days while maintaining its conformational stability during the period of study

Summary

Introduction

Therapeutic proteins are difficult to be administered orally because they are liable to degradation by the harsh gastric environment, hepatic metabolism and short half-lives thereby necessitating frequent administration of high doses by parenteral route (Cleland et al, 2001; Fu et al, 2000; Robinson and Talmadge, 2002). This may lead to major compliance issues in case of geriatric and pediatric patients on replacement therapy. Intra-nasal administration of deslorelin is ineffective and inconstant, with only 4 to 21% being available relative to s.c. or i.v. injection, necessitating frequent large doses (Gudmundsson et al, 1984)

Methods

Results

Conclusion