Effect of sintering on controlled release profile of diltiazem hydrochloride tablets prepared by melt granulation technique

Abstract

The study was designed to formulate and evaluate diltiazem hydrochloride wax matrix tablets for controlled release using sintering technique. Granules of diltiazem hydrochloride-wax were prepared by melt granulation technique. This was formed by triturating the drug powder with a melted carnauba wax (drug: wax ratio, 4.5:1). Matrix tablets of diltiazem hydrochloride-wax were prepared by compressing the drug-wax granules at constant pressure. The tablets were subsequently sintered at 60 and 70^oC for 1, 3 and 5h. The unsintered, sintered and commercial brand (CB) of sustained release tablets of diltiazem hydrochloride were evaluated for tablet hardness, friability and in vitro dissolution rate. Release kinetics and mechanism were confirmed by measuring the correlation coefficient (r-values) of the release data. The optimized formulation was characterized with Fourier-Transform Infrared (FTIR) spectroscopy to investigate any drug-excipient interaction. Generally, sintered tablets had a higher hydrophobicity than the unsintered tablets. Controlled release of diltiazem hydrochloride-wax matrix tablets from the sintered tablets depended on the temperature and time of sintering. For instance, tablet formulation sintered at 60 and 70°C for a period of 3h gave maximum release (m_∞), time to attain maximum release (t_∞) and dissolution rate (m_∞/t_∞) of 94%, 91.2%, 6h, 12h, 15.7%h^-1 and 7.6%h^-1 respectively. Results showed that cumulative percent of drug released from the optimised formulation was comparable to that of CB. There was no chemical interaction between the drug and excipients before and after sintering. This indicates that sintering technique can be used to increase the hydrophobicity of formulations and hence increase drug retardation.