Performance and characteristics of controlled release matrices composed of hydroxpropylmethylcellulose and other polymers
This thesis examines the use of hydroxypropylmethylcellulose (HPMC), sodium carboxymethylcellulose (NaCMC) or ethylcellulose, alone or in combination with other adjuncts, to control the release of propranolol hydrochloride from matrices. Gels were characterized by U tube viscometry and their cloud points of gels. The properties of polymers and their mixture in matrices or in gels were investigated by differential scanning calorimetry (DSC). Compendial dissolution methodology was used to determine drug release from matrices and their release exponents. Propranolol hydrochloride increased the solubility of HPMC and altered the water distribution in their gels. The release of propranolol hydrochloride from HPMC matrices was dependent on the square root of time. Release exponents were - 0.6, indicating that diffusion and erosion contributed to drug release. The release rates of propranolol hydrochloride from NaCMC matrices decreased as the NaCMC content increased. Addition of propranolol hydrochloride to NaCMC gels produced an insoluble complex which, in matrices, controlled the drug release. The interaction between propranolol hydrochloride and NaCMC was confirmed by DSC and dialysis. The viscosity grade of NaCMC affected the drug release. NaCMC matrices showed fast erosion. The release of sodium ions from matrices containing NaCMC was enhanced propranolol hydrochloride, confirming the occurrence of the interaction in matrices. The release of propranolol hydrochloride from NaCMC matrices was not dependent on either the square root of time or time. Large increases in release rates from matrices containing NaCMC in acidic media implied the polymer was unable to gel provide or a sustained release of propranolol hydrochloride at low pH. A synergistic increase in viscosity in gels containing HPMC and NaCMC probably played a minor role in propranolol release from matrices containing both polymers. NaCMC decreased the cloud point of HPMC. Drug release from matrices containing HPMC and NaCMC was very complicated, but zero order release was achieved from matrices containing 285 mg of 1: 3 HPMC : NaCMC. Addition of HPMC to NaCMC matrices suppressed an initial burst release of propranolol. The release of propranolol hydrochloride from matrices containing HPMC and NaCMC was dependent on pH. Ethylcellulose was capable of binding = 14% w/w water. Matrices containing ethylcellulose 7 cP (<125 pm) showed lower release rates than matrices containing ethylcellulose 10 cP, or at greater particle sizes. Compaction pressure generally did not affect drug release. The release exponent from matrices containing ethylcellulose was 0.44 - 0.49 indicating diffusion predominated drug release. Admixture of ethylcellulose with HPMC did not change the release exponent (0.59 < n < 0.61) from that of HPMC alone, whereas the exponents of NaCMC:ethylcellulose matrices was altere. Addition of ethylcellulose to HPMC increased the initial uptake of water. The incorporation of a complex of propranolol and β-cyclodextrin failed to retard the release of drug or alter the release exponent.