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

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 μl/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 μm 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, M_t/M_α = k₂tⁿ, for the initial phase and by the square-root model of Higuchi, Q_t = k₁ t^1/2 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.

Key Words:

• Eudragit
• Microspheres
• acetylsalicylic acid
• solvent-partition
• aspirin controlled drug release