Developing In Situ-Forming Implant for One Month Delivery of Triptorelin Acetate (Investigation the role of Polymer Type on Membrane Formation)
Paper ID : 1194-MST2015-FULL
Sepideh Farokhnia1, Hamid Mobedi *2, Milad Jafari-Nodoushan3
1Research and Development Department, Varian Pharmed Pharmaceutical Co., P.O. Box 14965/115, Tehran, Iran
2Tehran, Pajoohesh Blvd
3Pazhoohesh Blvd, Km 15, Tehran- Karaj Hwy,Tehran, I.R. Iran .
Triptorelin is a gonadotropin-releasing hormone (GnRH) analogue with enhanced affinity for GnRH receptors and a prolonged half-life due to its resistance to enzymatic degradation. It is indicated for treatment of prostate cancer, endometriosis, uterine fibroids and precocious puberty. The sustained-release formulation of this molecule is advantageous in conditions requiring chronic hormone suppression.
In situ forming implants (ISI) based on phase separation by solvent exchange represents an attractive alternative to conventional preformed implants and microparticles for parenteral applications. The solution, consisting of a biodegradable polymer dissolved in a biocompatible water-miscible solvent, along the dissolved/suspended drug, is injected subcutaneously. Upon injection into an aqueous environment, the solution undergoes phase inversion, forming the drug encapsulating membrane. Morphological details of produced implant and subsequently it drug release and degradation rate vary depending on the nature of the mass transfer and phase separation processes.
In this study, an in situ forming implant was developed for delivering triptorelin over one month period. In this regard a series of formulation were prepared and effect of different type of PLGA polymers and their combination in different compositions were investigated. The in vitro release study was performed and the best formulation subjected to in vivo studies on New Zealand white male rabbits. In next step the formulation further examined in healthy volunteers and their testosterone blood level measured as response. The results showed that the selected formulation has good efficacy in lowering testosterone below the castration level.
Triptorelin, In situ forming, PLGA, In vitro, In vivo
Status : Paper Accepted (Poster Presentation)