WATER-UPTAKE IN TO POLYANHYDRIDE DEVICES - KINETICS OF UPTAKE AND EFFECTS OF MODEL COMPOUNDS INCORPORATED, AND DEVICE GEOMETRY ON WATER-UPTAKE

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 wanted to test the hypothesis that polyanhydrides, spec ifically poly(fatty acid dimer-sebacic acid; FAD-SA) undergo pure surf ace erosion. If P(FAD-SA) does indeed undergo pure surface erosion, ve ry little water should be present in the device since the polymer is h ydrophobic and hydrolyzed on contact with water. An understanding of w ater uptake is also necessary to predict the stability and release of the incorporated drug. The specific aims of this study were to establi sh the rate of water uptake into P(FAD-SA) devices of cylinder and dis k shapes at various pH conditions, and to study the effect of loaded m odel drug compounds (having different molecular size, aqueous solubili ty and dissolution rate) on water uptake. The model compounds included : mannitol, inulin and stearic acid, loaded at 10% (w/w) in disk-shape d devices. Water uptake was estimated from the amount of tritiated wat er found in the devices after they were soaked and gently mixed with b uffers (pH 1-9) containing tritiated water (1 mu Ci/ml) at various tim e intervals. The results showed that water uptake by the device is a f unction of pH (pH 9 > pH 7.4 >>> pH 1-5). Significantly higher amount of water was taken up at pH 7.4 and 9.0 (8-9% (v/v) for cylindrical de vices, 15-25% (v/v) for disk-shaped device in 2 weeks), compared to le ss than 5% (v/v) uptake between pH 1 and 5. Disk-shaped devices showed a faster uptake rate compared to cylinder-shaped devices due to their higher surface area to volume ratio. The loaded compounds had no sign ificant effect on either the water uptake profile or water uptake kine tics at all pH values examined. From the large amount of water (up to 20% (v/v)) found in the devices at pH 7.4 and pH 9.0, it appears that P(FAD-SA) does not undergo pure surface erosion. The photomicrographs of the devices at various stages of water uptake showed channels on th e rough surface indicative of bulk erosion rather than pure surface er osion.