Preparation and in vitro release kinetics of ivermectin sustained-release bolus optimized by response surface methodology

PeerJ. 2018 Jul 31:6:e5418. doi: 10.7717/peerj.5418. eCollection 2018.

Abstract

Sustained-release formulations of ivermectin (IVM) are useful for controlling parasitic diseases in animals. In this work, an IVM bolus made from microcrystalline cellulose (MCC), starch and low-substituted hydroxypropyl cellulose (LS-HPC) was optimized by response surface methodology. The bolus was dissolved in a cup containing 900 mL of dissolution medium at 39.5 °C, under with stirring at 100 rpm. A quadratic model was formulated using analysis of variance according to the dissolution time. The optimized formulation of the bolus contained 8% MCC, 0.5% starch, and 0.25% LS-HPC. The length, width, and height of the prepared IVM bolus were 28.12 ± 0.14, 16.1 ± 0.13, and 13.03 ± 0.05 mm, respectively. The bolus weighed 11.4842 ± 0.1675 g (with a density of 1.95 g/cm3) and contained 458.26 ± 6.68 mg of IVM. It exhibited in vitro sustained-release for over 60 days, with a cumulative amount and percentage of released IVM of 423.72 ± 5.48 mg and 92.52 ± 1.20%, respectively. The Korsmeyer-Peppas model provided the best fit to the dissolution release kinetics, exhibiting an R2 value close to 1 and the lowest Akaike Information Criterion among different models. The parameter n (0.5180) of the Korsmeyer-Peppas model was between 0.45 and 0.89. It was demonstrated that the release mechanism of the IVM bolus followed a diffusive erosion style.

Keywords: Bolus; Dissolution kinetic model; Ivermectin; Korsmeyer–Peppas; Sustained-release.

Grants and funding

This work was granted support from the National Key Research and Development Program of China (2016YFD0501306). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.