Journal of Microencapsulation, Vol.12, No.3, 287-305, 1995
PHYSICOCHEMICAL EVALUATION OF ACETYLSALICYLIC ACID-EUDRAGIT(R) RS100 MICROSPHERES PREPARED USING A SOLVENT-PARTITION METHOD
Controlled release homogeneous matrix microspheres containing acetylsalicylic acid (ASA) were prepared by a simple mechanical process using Eudragit(R) 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 mu l/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 mu m 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(infinity) = k(2)t(n), for the initial phase and by the square-root model of Higuchi, Q(t) = k(1)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.
Keywords:EUDRAGIT RS-MICROCAPSULES;DRUG RELEASE;SUSTAINED-RELEASE;MICROENCAPSULATION;POLYACRYLATE;INDOMETHACIN;DISPERSIONS;DIFFUSION;POLYMERS;MATRIX