Physico-chemical evaluation of acetylsalicylic acid-Eudragit® RS100 microspheres prepared using a solvent-partition method

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Abstract
Controlled release homogeneous matrix microspheres containing acetylsalicylic acid (ASA) were prepared by a simple mechanical process using Eudragit RS100 as the matrix polymer. A drug-polymer solution in a binary solvent of methylene chloride/acetone (9:1) was prepared and infused at a rate of 15 microliters/min as small droplets into a flowing stream of mineral oil where partition of the solvent occurred. A series of experiments was conducted in which the polymer to drug ratio in the infusion solution was fixed at 5:1, 4:1, 3:1 or 2:1 while varying the infusion solution viscosity by altering the infusion solution total solids concentration. Results indicate that microsphere mean particle size was maintained at 200-300 microns once the infusion solution viscosity exceeded 2 cps. The physical state of the ASA incorporated into the microspheres, as confirmed by SEM and thermal analysis, was amorphous in nature until a drug loading of 24% was reached. Drug loading for each polymer to drug ratio increased in a proportional manner with respect to the initial drug concentration of the infusion solution. Dissolution release profiles were found to be biphasic and best analysed according to the semi-empirical equation of Ritger-Peppas, Mt/Mx = k2tn, for the initial phase and by the square-root model of Higuchi, Qt = k1t1/2 for the latter phase. This difference was attributed to the lack of a barrier effect to the drug diffusion process during the latter dissolution phase when the microspheres are fully hydrated.

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