Modeling the kinetics of release of octreotide from long-acting formulations injected intramuscularly in rabbits

J Pharm Sci. 2000 Sep;89(9):1123-33. doi: 10.1002/1520-6017(200009)89:9<1123::aid-jps4>3.0.co;2-k.

Abstract

Long-acting repeatable formulations (LAR) based on polymeric microspheres were manufactured to deliver octreotide, an octapeptide analogue used in acromegaly. We developed a model to describe the complex triphasic concentration versus time profile observed in rabbits after intramuscular (i.m.) injection of these LAR formulations. A 5-mg x kg(-1) dose of octreotide in a reference LAR formulation was given im to eight rabbits; two groups of four rabbits each received a different formulation. In each animal, 26 blood samples were taken over 49 days. Concentrations of octreotide were assayed by radioimmunoassay. A model describing the concentration profile was developed. Octreotide release was described using the succession of an exponential model, a semiempirical non-Fickian model, and a delayed Weibull model. Parameters were estimated using nonlinear regression, first for the eight rabbits that received the reference formulation and then for the other eight animals. The model provides an adequate description of the concentration versus time profile for the three formulations. For the reference phase, erosion accounted for 87% of total drug release. The formulation encapsulating an octreotide-acetate complex showed a prolonged diffusion phase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorption
  • Animals
  • Biocompatible Materials / administration & dosage
  • Biocompatible Materials / chemistry
  • Biocompatible Materials / pharmacokinetics
  • Chemistry, Pharmaceutical
  • Delayed-Action Preparations
  • Diffusion
  • Drug Carriers
  • Hormones / administration & dosage
  • Hormones / chemistry
  • Hormones / pharmacokinetics*
  • Injections, Intramuscular
  • Lactic Acid / administration & dosage
  • Lactic Acid / chemistry
  • Lactic Acid / pharmacokinetics
  • Male
  • Mathematical Computing
  • Microspheres
  • Models, Biological*
  • Nonlinear Dynamics
  • Octreotide / administration & dosage
  • Octreotide / chemistry
  • Octreotide / pharmacokinetics*
  • Polyglycolic Acid / administration & dosage
  • Polyglycolic Acid / chemistry
  • Polyglycolic Acid / pharmacokinetics
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polymers / administration & dosage
  • Polymers / chemistry
  • Polymers / pharmacokinetics
  • Rabbits
  • Surface Properties

Substances

  • Biocompatible Materials
  • Delayed-Action Preparations
  • Drug Carriers
  • Hormones
  • Polymers
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Octreotide