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