title: Sustained-release delivery of octreotide from biodegradable polymeric microspheres.
abstract: The study reports on the drug release behavior of a potent synthetic somatostatin analogue, octreotide acetate, from biocompatible and biodegradable microspheres composed of poly-lactic-co-glycolic acid (PLGA) following a single intramuscular depot injection. The serum octreotide levels of three Oakwood Laboratories formulations and one Sandostatin LAR(®) formulation were compared. Three formulations of octreotide acetate-loaded PLGA microspheres were prepared by a solvent extraction and evaporation procedure using PLGA polymers with different molecular weights. The in vivo drug release study was conducted in male Sprague-Dawley rats. Blood samples were taken at predetermined time points for up to 70 days. Drug serum concentrations were quantified using a radioimmunoassay procedure consisting of radiolabeled octreotide. The three octreotide PLGA microsphere formulations and Sandostatin LAR(®) all showed a two-phase drug release profile (i.e., bimodal). The peak serum drug concentration of octreotide was reached in 30 min for all formulations followed by a decline after 6 h. Following this initial burst and decline, a second-release phase occurred after 3 days. This second-release phase exhibited sustained-release behavior, as the drug serum levels were discernible between days 7 and 42. Using pharmacokinetic computer simulations, it was estimated that the steady-state octreotide serum drug levels would be predicted to fall in the range of 40-130 pg/10 μL and 20-100 pg/10 μL following repeat dosing of the Oakwood formulations and Sandostatin LAR(®) every 28 days and every 42 days at a dose of 3 mg/rat, respectively.
authors.affiliation: Department of Pharmaceutical Sciences-Drug Development Division, University of Kentucky College of Pharmacy, Lexington, 40536-0596, USA.
authors.forename: Yun-Seok
authors.initials: YS
authors.lastname: Rhee
authors.forename: MinJi
authors.initials: M
authors.lastname: Sohn
authors.forename: Byung H
authors.initials: BH
authors.lastname: Woo
authors.forename: B C
authors.initials: BC
authors.lastname: Thanoo
authors.forename: Patrick P
authors.initials: PP
authors.lastname: DeLuca
authors.forename: Heidi M
authors.initials: HM
authors.lastname: Mansour
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical; D003198:Computer Simulation; D004337:Drug Carriers; D004339:Drug Compounding; D004343:Drug Implants; D007273:Injections, Intramuscular; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D008863:Microspheres; D008954:Models, Biological; D015282:Octreotide / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D004337:Drug Carriers; D004343:Drug Implants; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D015282:Octreotide