Drug-Delivery by Ion-Exchange: Part IIII: Interaction of Ester Pro-Drugs of Propranolol with Cationic Exchange Resins

The interaction of a series of O-n-acyl propranolol prodrugs with strong cation exchange resins is reported and various variables which control loading and release profiles have been investigated. pH has little practical effect on the loading efficiency under the conditions used but standardisation of experimental details for the measurement of in vitro liberation profiles must be undertaken. In particular, stirring speeds of 200-300 rpm were necessary to ensure the independence of release profile and agitation. Additionally, the dissolution medium may not provide sink conditions throughout the full dissolution process if pH variation does not take into account solubility differences between analogues. Ionic strength also influences release rates and attempts to examine the effects of pH must also control this variable. The proportion of cross-linking agent in the resin plays an important role. Increasing the cross-linking delays considerably the release of drug from the matrix and is a useful parameter in optimising controlled delivery. The loading efficiency of the resin is reduced, however, as the cations are excluded from parts of the resin due to a reduction in pore diameter. In contrast, the particle size of the resin has little influence upon loading efficiencies but larger particles significantly delay the release of drug. The effect of 0-n-acyl chain-length on the loading and release profiles was determined by molecular size. As groups increased in size the loading was inhibited and release rates were reduced. Again, this enables some control of release profiles but the approach is most suitable for drugs which are active at low doses which allow full use of these variations without the necessity for large amounts of resin in the delivery system.