Drug Release Modulation from Cross-Linked Calcium Alginate Microdiscs, 2: Swelling, Compression, and Stability of the Hydrodynamically-Sensitive Calcium Alginate Matrix and the Associated Drug Release Mechanisms

Cross-linking through ionotropic gelation of sodium alginate with calcium chloride was employed to encapsulate the model drug indomethacin into the swellable multiple-unit calcium alginate microdisc delivery system to control its release. The influence of dissolution variables/hydrodynamics on drug release behavior was evaluated in accordance with the standard USP23 apparatus I and II, as well as the unofficial rotating bottle method. Drug release rates from the different methods were shown to be inter-and intradependent on the agitation rate as a result of the swellable, erosion-sensitive nature of the calcium alginate matrix. Preliminary compression studies indicated that the decrease in drug release was due to the hindrance of microdisc swelling as a result of the formation of a more dense and compact matrix, as observed from scanning electron microscopy. Maximum degree of swelling of the calcium alginate microdiscs (83.35 +/- 0.98%) occurred in <6 h of exposure to phosphate buffer, pH 6.2. The drug-encapsulated microdiscs were filled into no. 2 gelatin capsules and subject to stability testing at room temperature (21 +/- 1 degrees C), 40 degrees C, 37 degrees C with 80% relative humidity and at low temperature (5 +/- 1 degrees C). An evaluation of the potency, moisture content, and drug release behavior over a 3-month period provided evidence of a stable drug delivery system under all storage conditions. Mathematical analysis of dissolution data confirmed that the mechanism of drug release from the swellable microdiscs was modulated by mixed swelling/erosion following intermediate zero/first-order diffusion processes.