Composite Poly(vinyl alcohol) Beads for Controlled Drug Delivery

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Abstract
A new method of preparing composite poly(vinyl alcohol) (PVA) beads with a double-layer structure has been developed, which involves a stepwise saponification of suspension polymerized poly (vinyl acetate) (PVAc) beads and subsequent stepwise cross-linking of the PVA core and shell with glu-taraldehyde. This process results in PVA beads with thin, highly cross-linked outer shells and lightly cross-linked inner cores of different degrees of cross-linking. In addition to structural characterization of the polymer based on equilibrium swelling measurements, the kinetics of water swelling and drug release from these beads were studied at 37°C using acetaminophen and proxyphylline as model drugs. The results show that the outer shell functions as a rate-controlling membrane upon increasing its cross-linking ratio, X, above 0.47. This aspect is reflected in the observed diffusional time lags and constant-rate regions during swelling and drug release. Based on observed time lags, the diffusion coefficient of water through the outer PVA shell with a high cross-linking ratio of X = 0.5 is estimated to be at least six times higher than that of acetaminophen and proxyphylline. In addition, drug diffusion coefficients in the lightly cross-linked PVA core appear to be at least 10 times larger than that in the highly cross-linked outer shell. At lower shell cross-linking ratios (X < 0.4), the diffusional time lags appear to be absent and the diffusion profiles are apparently first-order (Fickian) in nature.

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