PROPERTIES CONTROLLING THE DIFFUSION AND RELEASE OF WATER-SOLUBLE SOLUTES FROM POLY(ETHYLENE OXIDE) HYDROGELS .2. DISPERSION IN AN INITIALLY DRY SLAB

The mechanisms which control the release of dispersed water-soluble dr ugs from an initially dry hydrogel are complex. The release profile de rives from a combination of several contributing factors which may cha nge with time at different rates. It has been possible to isolate cont rolling factors and investigate their individual contributions to the release kinetics. The hydrogels presented in this paper owe their hydr ophilicity to their poly(ethylene oxide) content. They swell and can a bsorb up to three times their dry weight in water. Having a glass tran sition temperature (T(g)) below body temperature they are essentially different to those studied theoretically or experimentally, by other g roups, which have T(g) values above body temperature and are initially glassy. A range of diffusates was studied ranging from low water-solu ble prostaglandin E2 to highly water-soluble lithium chloride. Device geometry was restricted to approximations to infinite slabs with more than 85% total surface area over the top and bottom surfaces so that r elease was predominantly one-dimensional and the controlling variable was thickness. The increase in surface area with time, drug-solubility in the water-swelling matrix and the presence of crystallinity were s hown to be important factors governing the profile and level of releas e rate with time. It was observed that the release profile could be se parated into three parts, the most important being the middle section from early in the release until at least the half-life time. This peri od could be characterized by the exponential time function, t(n). The diffusional exponent, n, is an important indicator of the release mech anism and ranged from 0.79 to 1, i.e. good anomalous to zero order. Th is is a highly desirable range of values for controlled release device s. The value of n decreases at late-time. The very early-time release can also show a burst or lag effect depending on the diffusate solubil ity and its loading in the xerogel. Key words: Xerogel; hydrophilicity ; equilibrium water content; dissolution; exponential function; surfac e area.