INFLUENCE OF IONIC-STRENGTH ON MATRIX INTEGRITY AND DRUG RELEASE FROM HYDROXYPROPYL CELLULOSE COMPACTS

Hydroxypropyl cellulose (HPC) is commonly used in formulating hydrophilic sustained release matrix tablets. Since ions can affect the degree of hydration and solution viscosity of HPC, there was concern whether these ionic changes will affect the drug release rate of tablets containing HPC. The objective of this study was to determine the effect of ionic strength solutions on the matrix integrity and drug release from HPC sustained release matrix compacts. In addition, the influence of HPC particle size and molecular weight on this system was investigated. Pure HPC and drug/HPC compacts were manufactured on an instrumented tablet press and tested for disintegration and dissolution under various ionic strength NaCl solutions. At ionic strengths less than 0.5, the compacts underwent swelling and gelation without any disruption of the matrix integrity or increased drug release. At 0.5-1.0 ionic strengths, certain types of HPC disaggregated and released drug rapidly. Above 1.0 ionic strengths, the compacts did not disaggregate, although release rates remained high for the high molecular weight HPCs. Fine particle size HPC was more resistant to the influences of ionic strength changes as was lower molecular weight HPC. The results of this study indicate that at normal physiological ionic strengths HPC compacts remain intact and release drug slowly.