Sustained-release delivery of octreotide from biodegradable polymeric microspheres

Yun Seok Rhee, Minji Sohn, Byung H. Woo, B. C. Thanoo, Patrick P. Deluca, Heidi - Mansour

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1293-1301
Number of pages9
JournalAAPS PharmSciTech
Volume12
Issue number4
DOIs
StatePublished - Dec 2011
Externally publishedYes

Fingerprint

octreotide
biodegradability
Octreotide
Microspheres
glycolic acid
blood serum
drugs
milk
Serum
acetates
Pharmaceutical Preparations
somatostatin
rats
radioimmunoassays
computer simulation
pharmacokinetics
evaporation
polymers
Intramuscular Injections
Somatostatin

Keywords

  • in vivo drug release
  • pharmacokinetic simulation
  • PLGA microspheres
  • polypeptide/protein drug delivery
  • single depot injection

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Sustained-release delivery of octreotide from biodegradable polymeric microspheres. / Rhee, Yun Seok; Sohn, Minji; Woo, Byung H.; Thanoo, B. C.; Deluca, Patrick P.; Mansour, Heidi -.

In: AAPS PharmSciTech, Vol. 12, No. 4, 12.2011, p. 1293-1301.

Research output: Contribution to journalArticle

Rhee, Yun Seok ; Sohn, Minji ; Woo, Byung H. ; Thanoo, B. C. ; Deluca, Patrick P. ; Mansour, Heidi -. / Sustained-release delivery of octreotide from biodegradable polymeric microspheres. In: AAPS PharmSciTech. 2011 ; Vol. 12, No. 4. pp. 1293-1301.
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