The influence of microencapsulation using Eudragitr` RS100 on the hydrolysis kinetics of acetylsalicylic acid

Abstract

Homogeneous Eudragit® RS100 matrix microspheres containing molecularly dispersed acetylsalicylic acid (ASA) were prepared in order to investigate the effect of encapsulation on the decomposition rate of a hydrolytically susceptible drug. ASA-loaded microspheres of this non-eroding polymer matrix were analysed at predetermined time points following immersion of the microspheres in temperature controlled buffer systems at pH 1.2 or pH 12.1 at 30, 40 or 50°C. The mass balance of the total amount of solutes (ASA and SA) initially located within the microsphere interior was equal to the sum of the amount of solutes remaining in the microsphere interior and the amount of solutes in the aqueous phase at any time during the course of the study. Each analysis involved the quantitation of four species; the drug and decomposition product, salicylic acid (SA), in both the microsphere phase and the external aqueous phase. A simple model system using first-order rate approximations for the concurrent Fickian diffusion and hydrolysis decomposition of the drug resulted in a multi-exponential expression which adequately described the time-course profile of the drug. SA-loaded microspheres were used as a control under similar conditions to determine the magnitude of the contribution of microsphere phase hydrolysis of ASA to the overall rate of drug loss from the microspheres. Results indicated that microsphere phase hydrolysis of ASA was minimal. Even after 900 h of immersion in pH 12.1 buffer some ASA remained within the micro-sphere. It is postulated that the matrix incorporated drug is essentially shielded from hydrolytic attack until it is liberated into the external aqueous environment. Electrostatic association of the drug with the charged quaternary residues in the polymer along with the limiting availability of water within the micro-sphere may be responsible for the observed stability of ASA in aqueous swollen ASA-loaded Eudragit® microspheres.

Key Words:

• Microsphere
• salicylic acid
• pseudo first-order
• multi-exponential
• diffusion drug release
• Eudragit®
• Acetylsalicylic acid