Parameters to be Considered in the Simulation of Drug Release from Aspirin Crystals and their Microcapsules

Fe Eichie,Rs Okor

doi:10.4314/tjpr.v1i2.14590

Abstract

Purpose: Drug microparticles may be microencapsulated with water-insoluble po lymers to obtain controlled release, which may be further determined by the pa rticle d istribution. The purpose o f t his s tudy was to de termine the drug release pa rameters needed for the theoretical prediction of the release profiles of single aspirin crystals and their microcapsules. Method: Four single crystals of aspirin of varied weight and orthorhombic in shape or their microcapsules also of varied weights were randomly selected for the study. The microcapsules were walled with an acrylatemethacrylate copolymer ( wall thickness, 11 i m). The following parameters were evaluated: the order of release, the dissolution rate constant, k (crystals), the diffusion coefficient, D (microcapsules), the maximum release m∞ and time to attain it t∞. These parameters were in turn used to simulate the release profiles of hypothetical single particles of a wide range size distribution, 0.3 ‐ 1.4 mm at 0.1mm intervals. Results: The e mpirical single crystals exhibited an initial zero o rder ( 93%; dissolution constant = 4.4 min -1 ) followed by a first order release (6%; dissolution constant = 0.38 min -1 ). Maximum release from each of the crystals was 99% of the initial particle weight; thus m∞ was a constant fraction of the initial particle weight. A zero order release consistent with a Fickian diffusion model was displayed b y the single microcapsules (diffusion coefficient, 5.4x10 -4 mm 2 min -1 ). At same particle weight the release parameters m∞, t∞, and the slopes of the rate order plots compared favourably with the theoretical data. Conclusion: The study indicates that the empirical release data on a few single particles can be used to predict the release profiles of single particles of a wide range of size distribution. This finding may be exploited in the prediction of drug release from polydisperse systems.

Highlights

The selection by trial and error of formulations that will give optimal performance is tedious but expensive, simulation has become important in optimisation in formulation studies
In the present study a few representative particles were used to determine the release parameters, which could in turn be used in the simulation of drug release from several single particles. Such theoretical data on single particles can in turn be used to simulate releases from ensembles of particles of an accidental or a predetermined distribution. In this first part of the study, we present how the empirically determined parameters were used to simulate the release profiles of hypothetical single particles
A double phase kinetic of an initial zero order followed by a first order release was considered

Summary

Introduction

The selection by trial and error of formulations that will give optimal performance is tedious but expensive, simulation has become important in optimisation in formulation studies Such simulations involve the development of mathematical models[1,2,3,4] or use of well known (i.e. previously determined) constants[3] which have been referred to here as the drug release parameters. Perhaps the most common design is that whereby the drug particles acting as core material are coated with a polymer as wall material[4,5,6] The purpose of such a device is to control either the rate and/or the onset of the release. Various studies[5,6,7,8] showed that drug release from such polydisperse systems follow a first order kinetic

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Conclusion