Release Characteristics of Diltiazem Hydrochloride Wax-Matrix Granules – Thermal Sintering Effect

The aim of this study was to investigate the release characteristics of matrix (non-disintegrating) granules consisting of diltiazem hydrochloride (model drug) and glyceryl behenate (a wax matrix forming polymer) for sustained release application using sintering technique. The granules of diltiazem hydrochloride-wax matrix were prepared by melt granulation technique. This was formed by triturating the drug powder with a melted glyceryl behenate (drug: wax ratio, 3:1). The granules were subsequently sintered at 60 and 70⁰C for 1, 1.5 and 3h. The unsintered and sintered wax matrix granules of diltiazem hydrochloride were evaluated for physicochemical parameters and in vitro dissolution studies. The dissolution data were subjected to analysis using different mathematical models namely – zero order flux, first order, Higuchi square root of time, then Korsmeyer and Peppas model. Fourier-Transform Infrared Spectroscopy (FTIR) was carried out to investigate any chemical interactions between the drug and the added recipients before and after sintering. There was increased drug release retardation of diltiazem hydrochloride-wax matrix granules with sintering. The retardation depended on the temperature and duration of sintering. For instance, formulations sintered at 60 and 70°C for a period of 1.5h gave maximum release (m_∞), time to attain maximum release (t_∞) and dissolution rate (m_∞/t_∞) of 96.1%, 95.2%, 5h, 9h, 19.2%h^-1 and 10.6%h^-1 respectively. The drug release was by Higuchi controlled diffusion mechanism and it followed Fickain diffusion mechanism (n<0.45). Sintering technique enhanced the extent of drug retardation from the systems studied. There was no chemical interaction between the model drug and the added recipients as shown in the FTIR studies.

Keywords
Thermal Sintering technique, sustained release, Fourier-Transform Infrared Spectroscopy