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The prime objective was to enhance the solubility of acyclovir through developing a stable and non-toxic graft structure of β-cyclodextrin-g-poly (AMPS) hydrogel microparticles. Grafting was carried out successfully by applying aqueous free radical polymerization technique. N, N′-methylene bisacrylamide (MBA) and ammonium persulfate (APS) were used as crosslinking agent and initiator, respectively. These were characterized for %EE and product yield, solubility studies, FT-IR, DSC, TGA, PXRD, SEM, TEM, EXD, Zeta size and Zeta potential, swelling studies and in-vitro release studies. pH independent swelling and release was observed at pH 1.2 and pH 7.4 but slightly better results were seen at pH 7.4. Solubility of ACV was significantly improved, i.e. pH 1.2 (10.66 folds), pH 7.4 (8.90 folds) and in water (9.21 folds). Release data followed first order kinetics with non-Fickian (anomalous) diffusion release. In …