Sustained-Release Delivery of Octreotide from Biodegradable Polymeric Microspheres

Abstract

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-coglycolic 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.KEY WORDS: in vivo drug release; pharmacokinetic simulation; PLGA microspheres; polypeptide/ protein drug delivery; single depot injection.

Population Pharmacokinetics of an Extended-Release Formulation of Exenatide Following Single- and Multiple-Dose Administration

“…Exenatide plasma concentrations were assessed at 23 time points over the duration of the trial. Specific collection times included a rich sampling period (0.25, 0.5, 1,2,4,8,12,16,24,30,36, and 48 h postinjection) to capture initial drug release, followed by sampling at 11 additional time points (collected at weekly visits from weeks 1 to 11). A total of 1054 concentration measurements from 47 patients were collected in the singledose study.…”

Polyhydroxyalkanoates, a family of natural polymers, and their applications in drug delivery

“…Biodegradable polymers are becoming increasingly prominent in medicine, with P(4HB) already approved as a material for sutures due to its desirable biodegradability and safety . PLGA is also a biodegradable polymer approved by the FDA, and drugs such as Sandostatin LAR® have been based upon it . However, the benefits of PHA biodegradation over PLGA such as lower acidity of degradation products and surface degradation means that there is great scope for using PHAs as agents for controlled drug release.…”

“…67 PLGA is also a biodegradable polymer approved by the FDA, 133 and drugs such as Sandostatin LAR ® have been based upon it. 134 However, the benefits of PHA biodegradation over PLGA such as lower acidity of degradation products and surface degradation means that there is great scope for using PHAs as agents for controlled drug release. This grants them future application in conditions such as delivery of antibiotics for chronic infection 58 and maintenance of serum concentrations of drugs with narrow therapeutic windows.…”

The Influence of Spray-Drying Parameters on Phase Behavior, Drug Distribution, and In Vitro Release of Injectable Microspheres for Sustained Release

“…These samples showed a very restricted drug release (4.9% after 4 h), which is not surprising because this water-insoluble polymer is well established as a matrix for sustained release formulations. [1][2][3]…”