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

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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.