Zero-order release hydrophilic matrix tablets of β-adrenergic blockers

Abstract

A simple technique of obtaining nearly zero-order release from hydrophilic matrix tablets till entire drug is released is reported. In this technique, non-ionic hydroxypropylmethylcellulose (HPMC) and anionic sodium carboxymethylcellulose (Na CMC) were mixed in an optimum ratio with drug and compressed into tablets. To exemplify this fact, β-adrenergic blockers, namely propranolol hydrochloride, metoprolol tartrate and alprenolol hydrochloride, were chosen as model drugs. When the ratio of drug: HPMC: Na CMC was 1:0.25:2.25 for propranolol hydrochloride, 1:1.25:1.25 for metoprolol tartrate and 1:2.08:2.92 for alprenolol hydrochloride, total drug is released in about 12 h at a nearly zero-order rate. By optimising the ratio between the drug and total gum and also the ratio between these two gums, the rates of advancement of swelling front into the glassy polymer (core) and the attrition of the rubbery state polymer (gel at tablet periphery) were made equal so that the diffusional path length for the drug remains nearly constant. Extent of zero-order drug release from tablets was confirmed by fitting the dissolution data from 60% onwards to the equation of Korsmeyer and Peppas (1983).