Drug Release Modulation from Cross-Linked Calcium Alginate Microdiscs, 1: Evaluation of the Concentration Dependency of Sodium Alginate on Drug Entrapment Capacity, Morphology, and Dissolution Rate

Abstract

Calcium alginate microdiscs were prepared by the gelification technique using sodium alginate as the precursor hydrophilic polymer and calcium chloride aqueous solution (1% w/v) as the cross-linking agent. Indomethacin, the model drug, was simultaneously encapsulated in the cross-linked swellable calcium alginate matrix. It was found that as the sodium alginate concentration was increased in the cross-linking reaction, there was a marked increase in drug entrapment capacity of the calcium alginate microdiscs. The 1% w/v indomethacin-calcium alginate microdisc formulation maximally entrapped 43.84% drug, while the 4% w/v formulation retained 92.18% drug. In addition, indomethacin release in phosphate buffer, pH 6.2, was markedly decreased as the precursor polymeric concentration was increased. The (80% for the 1% w/v formulation was approximately 3 h, while this value was extrapolated to 13.5 h for the 4% w/v formulation. A 1:1 combination of the 2 and 3% w/v formulations of the indomethacin-calcium alginate microdiscs provided bimodal, biphasic drug release characteristics similar to Indocid-R capsules. With the aid of scanning electron microscopy, it was demonstrated that the microdisc diameter also increased as the polymer concentration was increased. For example, the 1 and 4% w/v formulations had mean diameters of 1.26 and 2.17 mm, respectively. The micrographs also elucidated typical pore formation on the surface of the indomethacin-calcium alginate micro-discs, which suggested that the drug release mechanism is governed by swelling/erosion as well as partial diffusion. Density and surface area measurements of the indomethacin-calcium alginate microdiscs revealed that both dimensional characteristics decreased with increasing sodium alginate concentrations. A change in the drug:polymer ratio (1:1, 1:2, 1:2.5, 1:3, and 1:4) also resulted in microdiscs with higher potencies and slower dissolution rates. The above 4% w/v microdisc formulation was similar to the formulation containing the 1:4 drug:polymer fraction, in that both formulations were prepared from a 4% w/v sodium alginate solution. However, changing the polymer fraction proved more effective in decreasing the release of indomethacin from the calcium alginate microdiscs.