title: Formulation and evaluation of an in situ gel forming system for controlled delivery of triptorelin acetate.
abstract: The novel physical hydrogels composed of chitosan or its water soluble derivatives such as carboxymethyl chitosan (CMCh) and sodium carboxymethyl chitosan (NaCMCh) and opened ring polyvinyl pyrrolidone (OP-PVP) were used as a controlled delivery system for triptorelin acetate, a luteinizing-releasing hormone agonist. The in situ gel forming system designed according to physical interactions such as chains entanglements and hydrophilic attractions especially h-bonds of chitosan and/or NaCMCh and OR-PVP. In order to increase in situ gel forming rate the chitosan microspheres prepared through spray drying technique. The chitosan or NaCMCh/OR-PVP blends prepared at different ratios (0.05, 0.10, 0.12, 0.16, 0.20 and 0.24) and suspended in sesame oil as non-aqueous vehicle at different solid content (10-30%). The suitable ratio of polymers with faster in situ gel forming rate was selected for in vivo studies. The gel formation and drug release from the system was evaluated both in vitro and in vivo. In vitro and in vivo results were compared with Diphereline SR 3.75mg, a commercially available controlled delivery system of triptorelin. In vitro release studies showed a sustained release profile for about 192h with first order kinetics. In vivo studies on male rats by determination of serum testosterone were confirmed the acceptable performance of in situ gel forming system compared with Diphereline SR in decreasing the serum testosterone level for 35days, demonstrating the potential of the novel in situ gel forming system for controlled delivery of peptides.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Sh
authors.initials: Sh
authors.lastname: Abashzadeh
authors.forename: R
authors.initials: R
authors.lastname: Dinarvand
authors.forename: M
authors.initials: M
authors.lastname: Sharifzadeh
authors.forename: G
authors.initials: G
authors.lastname: Hassanzadeh
authors.forename: M
authors.initials: M
authors.lastname: Amini
authors.forename: F
authors.initials: F
authors.lastname: Atyabi
mesh_terms: D000818:Animals; D001682:Biological Availability; D001769:Blood / Q000187:drug effects; D048271:Chitosan / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000138:chemical synthesis / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D020100:Hydrogels / Q000138:chemical synthesis / Q000737:chemistry*; D007279:Injections, Subcutaneous; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008422:Materials Testing; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D011145:Polyvinyls / Q000737:chemistry; D016062:Porosity; D011759:Pyrrolidines / Q000737:chemistry; D051381:Rats; D011919:Rats, Inbred Strains; D012715:Sesame Oil / Q000737:chemistry; D012867:Skin / Q000187:drug effects / Q000473:pathology; D013055:Spectrophotometry, Infrared; D013737:Testis / Q000187:drug effects / Q000473:pathology; D013739:Testosterone / Q000097:blood; D017329:Triptorelin Pamoate / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D003692:Delayed-Action Preparations; D020100:Hydrogels; D011145:Polyvinyls; D011759:Pyrrolidines; C505150:poly(N-vinylpyrrolidine); D017329:Triptorelin Pamoate; D013739:Testosterone; D012715:Sesame Oil; D048271:Chitosan