https://centaur.reading.ac.uk/38544/10/1-s2.0-S0014305714004091-main%20%281%29.pdf

Biomedical applications of hydrogels: A review of patents and commercial products

Hydrogels: from controlled release to pH-responsive drug delivery.

Classification, processing and application of hydrogels: A review.

Preparation, structure and diffusional behavior of hydrogels in controlled release

Swellable matrices for controlled drug delivery: gel-layer behaviour, mechanisms and optimal performance.

Probing the mechanisms of drug release from hydrogels

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.

Composite poly(vinyl alcohol) beads for controlled drug delivery.

Using oxprenolol HC1 as a model drug, the effects of pH and buffer concentration on the swelling and drug release properties in cross-linked poly(methyl methacrylate-co-methacrylic acid) (PMMA/ MAA) beads have been investigated. The kinetics of swelling of such hydrophobic anionic gel beads from the dehydrated state appear to be governed primarily by a diffusion– ionization process which becomes more ionization-controlled at higher buffer concentrations. Within the range of ionic compositions studied, the swelling rate increases and the initial swelling/ionization front penetration becomes increasingly linear in time with increasing pH or buffer concentration of the swelling medium. The corresponding swelling bead diameter appears to reach an equilibrium value as soon as the penetrating ionization fronts meet at the center, suggesting a swelling equilibrium in the ionized shell due to rapid mechanical readjustment in the gel phase. At oxprenolol loading levels up to 15%, both the transient drug release and swelling bead diameter exhibit extended quasi-linear regions despite the inherent limitation of decreasing surface area at the penetrating front in the spherical geometry. In addition, both the drug release and the dimensional changes reach completion when the penetrating ionization fronts meet at the center, suggesting a true swelling-controlled drug release behavior.

Hydrophobic Anionic Gel Beads for Swelling-Controlled Drug Delivery

The effect of oxprenolol HCl loading on the kinetics of polymer swelling and drug release from suspension-polymerized poly(methyl methacrylate-co-methacrylic acid) (PMMA/MAA) beads has been studied in detail. Within the range of variables studied, the polymer swelling rate increases with buffer pH and concentration. And an ionization-controlled swelling mechanism (analogous to the relaxation-controlled mechanism) mechanism) seems to become more rate-limiting at higher buffer concentrations. At oxprenolol HCL loading levels below 17.8%, the drug release and associated dimensional changes (in pH 7.4) exhibit an extended quasi-linear region despite the inherent limitation of spherical geometry. At higher loading levels, the drug release becomes faster and first-order in nature. This is apparently a result of the transition from a dissolved to a dispersed system above a percolation threshold (15-18% loading in the present study). As a result of competition from processes such as the reduction of bead dimension due to drug release and the dimensional increase due to polymer swelling and osmotic contributions from the drug, the transient bead diameter increases monotonically during drug release at loading levels up to 25.6%, whereas upon further increasing the drug loading, the bead diameter goes through a maximum during the early drug release, which eventually increases again as a result of the slow but continuous increase in polymer swelling due to further ionization. In all cases, both the drug release and the dimensional changes approach completion as the penetrating ionization fronts meet at the center, indicating a true swelling-controlled behavior.

Effect of loading on swelling-controlled drug release from hydrophobic polyelectrolyte gel beads.

A new method of preparing large spherical PVA beads (up to 1.5 mm diameter) with a core-shell structure has been developed. This involves a stepwise saponification of suspension polymerized PVAc beads, followed by a stepwise crosslinking of the PVA core and shell with glutaraldehyde. The resulting composite PVA beads have thin, highly crosslinked outer shells and lightly to moderately crosslinked inner cores of different degrees of crosslinking. In addition to the characterization of structural parameters, the kinetics of solute release and the swelling dynamics, including the transient dimensional changes, have been investigated using proxyphylline as a model compound. © 1992 John Wiley & Sons, Inc.

Cherng-Ju Kim

Papers

Probing the mechanisms of drug release from hydrogels

Composite poly(vinyl alcohol) beads for controlled drug delivery.

Hydrophobic Anionic Gel Beads for Swelling-Controlled Drug Delivery

Effect of loading on swelling-controlled drug release from hydrophobic polyelectrolyte gel beads.

Synthesis and characterization of suspension‐polymerized poly(vinyl alcohol) beads with core–shell structure