Acta Pharm. 50 (2000) 229-238
The mechanisms of sustained release (SR) of drugs from tablet matrices prepared with poly(acrylic) acid polymers (Carbopols 940 and 941) were investigated to define the condition for selection of polymers for SR formulation development. A highly water soluble drug, chlorpheniramine maleate and a sparingly water soluble drug, theo- phylline hydrate were used as test drugs. The formulations were tested in simulated intestinal fluid (SIF) and simulated gastric fluid (SGF) without enzymes. The results obtained indicate that medium diffusion, swelling of the polymers, limited erosion of the matrix and the mass of drug loaded in the matrix determined the rate of drug release from SR matrix tablets. Rates of drug release and erosion of the matrix were not appreciably affected by the grade and/or the molecular mass of the polymers used. For drugs that are primarily released in the acidic region of the gastrointestinal tract (GIT), such as weakly acidic drugs exemplified by chlorpheniramine, Carbopol 940 seems to be most suitable, while for drugs that are released primarily in the alkaline region of the GIT, such as weakly basic drugs exemplified by theophylline, Carbopol 941 seems to be most suitable. Mathematical treatment of release data indicated that the poly(acrylic) acid polymers used for SR formulations should be selected on the basis of the release mechanisms operative for each drug studied in relation to the square and cube root release kinetics.
Keywords: poly(acrylic) acid, Carbopol 940, Carbopol 941, sustained release, medium diffusion, erosion rate, Hixson-Crowell release kinetics