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

Long-acting repeatable formulations (LAR) based on polymeric microspheres w ere manufactured to deliver octreotide, an octapeptide analogue used in acr omegaly. We developed a model to describe the complex triphasic concentrati on versus time profile observed in rabbits after intramuscular (im) injecti on of these LAR formulations. A 5-mg kg(-1) dose of octreotide in a referen ce LAR formulation was given im to eight rabbits; two groups of four rabbit s each received a different formulation. In each animal, 26 blood samples w ere taken over 49 days. Concentrations of octreotide were assayed by radioi mmunoassay. A model describing the concentration profile was developed. Oct reotide 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 tha t 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 accou nted for 87% of total drug release. The formulation encapsulating an octreo tide-acetate complex showed a prolonged diffusion phase. (C) 2000 Wiley-Lis s, Inc. and the American Pharmaceutical Association J Pharm Sci 89:1123-113 3, 2000.