EFFECTS OF MODEL COMPOUNDS WITH VARYING PHYSICOCHEMICAL PROPERTIES ONEROSION OF POLYANHYDRIDE DEVICES

Polyanhydrides are known as surface eroding biodegradable polymers sin ce they are hydrophobic, which is believed to prevent penetration of w ater into the bulk and hence only the labile bonds on the surface are hydrolyzed. We studied the effects of pH of the erosion medium and inc orporation of model compounds of various molecular size and aqueous so lubility on erosion of polyanhydride, specifically P(fatty acid dimer- sebacic acid; FAD-SA), as measured by weight loss of the device. The m odel compounds included: mannitol, inulin and stearic acid, loaded at 10% w/w in disk shaped devices. The devices were prepared by the melt- casting technique and weight loss accurately measured after agitating the devices in buffers (pH 1-9), and removing the device at selected t ime intervals and freeze-drying the device. All the devices, irrespect ive of the nature of the model compounds loaded, eroded rapidly at pH 9, 8-10 times faster than at pH 1-5 and 1.3-2 faster than at pH 7.4. T he pi-I-dependent nature of erosion was attributed primarily to the la bility of the anhydride linkages to the alkaline pH and higher solubil ity of the degradation product, SA, resulting in rapid diffusion and d issolution of SA out of the devices. Loading water-soluble compounds s uch as mannitol and inulin even at 10% w/w accelerated erosion rates a t all pH however, the effect was more significant at alkaline pH. In c ontrast, loading poorly water-soluble compounds such as stearic acid r etarded the erosion rates of devices at all pH except at pH 9, where s tearic acid is ionized and has higher aqueous solubility. The photomic rographs of the surface of the devices showed pores and channels surro unding island of material believed to be FAD, the pores and channels b eing bigger for the mannitol- and inulin-loaded devices. Based on thes e observations, it appears that water-soluble compounds will be releas ed rapidly creating pores and channels in the device, which will be pe netrated by water rapidly resulting in accelerated erosion. While poor ly water-soluble compound such as stearic acid retards erosion. Theref ore, erosion of biodegradable polyanhydride device is not simply a fun ction of polyanhydride chemistry but also involves water uptake, diffu sion and dissolution of the degradation products and hence is a functi on of both pH and the nature of the compounds incorporated into the de vice. From product development standpoint, influence of the drug's phy sicochemical characteristics on device erosion should be considered to determine its release characteristics and in vivo lifetime of the dev ice.