In-vitro Evaluations and Physical Characterizations of a Single Solid Dispersion Powder of Diltiazem Hydrochloride for the Development of Multiple Strengths Controlled Release Dosage Forms of the Drug.

摘要

Diltiazem hydrochloride is a calcium ion cellular influx inhibitor (slow channel blocker or calcium antagonist) Diltiazem is frequently used drug to treat hypertension (high blood pressure), angina (chest pain), and certain heart rhythm disorders. Controlled release formulations based on various technologies are currently available for once-a-day therapy. This study was undertaken to investigate the possibility of applying Solid Dispersion approach for developing controlled release formulations of this drug. Various rate-controlling polymers were evaluated in developing a single solid dispersion powder suitable for use in the formulation of multiple strengths dosage forms of the drug.;Different Solid Dispersions were prepared by solvent evaporation technique using single and multiple carrier systems. Samples equivalent to 120mg, 240mg and 360 mg of drug were evaluated for their in vitro drug release profiles according to the USP Dissolution Apparatus I. The Dissolution studies were conducted for 2 and 24 hours using SGF and SIF as the dissolution media respectively. A physical mixture of optimum formulation was also included for comparison purposes. The dispersion sample was aged for 1 month at various temperatures and evaluated for the drug release. In addition, the formulation was enlarged and studied for its stability to use on a commercial scale. Physical Studies including Differential Scanning Calorimetry, XRD and FTIR were carried out to characterize the Solid Dispersions.;Among all the samples evaluated, the solid dispersion containing Drug, Hydroxy Propyl Cellulose and Compritol 888 ATO at a weight ratio of 1:0.5:0.25 gave optimum controlled release dissolution profiles from 120mg, 240mg and 360mg strength formulations. Thought the amount of drug release was observed to be directly proportional to the dosage strengths, the % drug release vs. time yielded similar graphs, suggesting that dissolution patterns from all strengths are same. But the Physical Mixture of same formulation released 100% of drug in less than 60 minutes suggesting that it is not the polymer alone but the solid dispersion is controlling the drug release. The samples from Enlarged batches and stability studies also exhibited unaltered dissolution profiles from all strengths. The Dissolution data were treated with various kinetic orders and Higuchi's model provided the best fit suggesting that controlled release was diffusion based. The characterization studies indicated that there were no chemical interactions among the formulation ingredients.;Solid dispersion technique proved useful in formulating a single controlled release powder for its direct use in the development of 120mg, 240mg and 360mg dosage forms of Diltiazem Hydrochloride.