Formulation, Evaluation and Optimization of Sustain Release Matrix Tablet of Diltiazem HCL by Using Hydrophilic Natural Polymers

Abstract

Diltiazem HCl is a Calcium channel blocker which is used as anti-anginal and Class IV anti-arrhythmic drug. It is a drug of choice for stable and unstable angina pectoris, myocardial infarction, coronary artery spasm, cardiac arrhythmia, PSVT and hypertension. In this study, sustained release matrix tablets of Diltiazem HCl were prepared by wet granulation method. The formulation of each Diltiazem HCl sustained release matrix tablets is composed of two selected polymers i.e. chitosan and xanthan gum in alone or in combination. The other excipients used were lactose monohydrate for its diluent property, PVP K-30 as a binder and magnesium stearate and talc for lubrication. The weight of tablet was adjusted to 200 mg and each tablet contained 90 mg Diltiazem HCl. Total 9 batches (F1-F9) were prepared.Batch F1, F2 and F3 containing a single polymer i.e. xanthan gum in concentration of 15, 20 and 25% of total weight of the tablet. Batch F4, F5 and F6 containing a single polymer i.e. chitosan in concentration of 20, 30 and 40% of total weight of the tablet Batch F7, F8 and F9 containing combination of both polymers i.e. xanthan gum & chitosan in concentration of proportion ratios of 15:25, 17.5:25 and 20:25% of total weight of the tablet respectively. All the powders were passed through 100 mesh sieve after sieving. The drug & polymer were mixed uniformly, lactose was added to the above mixture and blend for 20 min. PVP K-30 dissolved in isopropyl alcohol (3%) was then added to the above mixture to form a wet mass. The wet mass was then passed through sieve no. 12 and granules were dried for 2 hrs at 55-600C. After drying, granules were passed through 16 mesh screen and resulting granules were mixed with magnesium stearate (1%) and talc (2%). The lubricated granules were compressed using flat faced punches (single punch tablet machine) into tablets. Compression pressure was adjusted during tableting of each formula to get the tablet hardness in the range of 6 to 6.5 kg/cm2. The compressed tablets of each formulation batch were then evaluated for tablet characteristics such as thickness, hardness, weight variation, friability and drug content. In this work showed that the drug release profile of formulation F8 resembles with that of marketed formulation. Hence formulation F8 containing combination of Xanthan gum and Chitosan in the concentration ratio of 17.5:25% (of the total weight of tablet) was considered as optimized formulation.