DESIGN AND EVALUATION OF A SUSTAINED-RELEASE AMINOPHYLLINE TABLET

An ethanolic granulation procedure was used to produce sustained -release tablets containing 225 mg aminophylline with ethylcellulose and paraffin wax or hydrogenated castor oil as retardant matrix. The former waxy material gave undesirable sticking problems during compression. Acceptable tablets were formed using the latter material, which after fusion at 95-degrees-C for 30 min, had an in-vitro release profile similar to the commercial product, ''Phyllocontin'' (Napp). Increasing the ratio of hydrogenated castor oil to ethylcellulose in the matrix or increasing its drug loading tended to give faster drug release. Application of up to 1% of a pH-independent polymethacrylate coating to the tablets for reduction of the burst-effect and for taste/odour masking, was associated with progressive reduction in drug release and was replaced by a non-controlled release coating not significantly affected by the level applied. The annealing treatment of tablet cores caused <2% volatilization of ethylenediamine and their drug content remained within compendial specification. Three of the fused and film-coated tablet batches with variable drug loading were examined in a panel of human volunteers, compared to ''Phyllocontin'' on acute dosing with 450 mg aminophylline. The product with 82.5% drug loading was bioequivalent to the commercial product, when a range of pharmacokinetic parameters were compared.