Formulation and In-Vitro Evaluation of Oral Sustained-Release Diclofenac Sodium Matrix Tablets Using Hydrophilic Polymer Blends

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A sustained effect of diclofenac is required for the treatment of some chronic conditions like rheumatoid arthritis, osteoarthritis and chronic pain. Sustained release matrix tablets of diclofenac sodium were formulated using the natural gums, xanthan gum and cashew gum together with the semi–synthetic release modifier, hydroxypropylmethylcellulose (HPMC). Crude and purified cashew gums were found to have satisfactory moisture content and insoluble matter. The gums were analysed for their rheological property and found to show pseudoplastic flow. Fifteen (15) different batches of matrix tablets of diclofenac sodium (dose 100 mg) were produced by wet granulation. Different ratios (100:0, 80:20, 60:40, 20:80, 0:100) of Xanthan: HPMC, Xanthan: Cashew and Xanthan: Cashew: HPMC were used. The flow properties of the granules and the physical properties of the compressed tablets namely, weight uniformity, crushing strength, drug content, friability and tablet thickness were evaluated. In – vitro release studies of the drug was performed in phosphate buffer, pH 7.5 over 24 hours with Voltaren Retard as the reference diclofenac sodium tablet. The granules produced had good flow properties as evidenced by their angles of repose, Hausner ratio and Carr’s index values. All the physical characteristics of the formulated tablets fell within acceptable limits. The swelling index of Batch 2 tablets containing only xanthan gum exhibited the highest swelling index followed by Batch 10 tablets containing xanthan and cashew gums in the ratio, 80:20. Different dissolution models were applied to the drug release data in order to evaluate the release mechanism and kinetics. The drug release data fitted well to the Higuchi square root model (R2 = 0.8308 – 0.9750).The n value obtained for most of the batches ranged from 0.45 to 0.89 which indicates that drug is released through an anomalous or non – Fickian transport. Overall, drug release was found to be a complex mixture of diffusion, swelling and erosion. The similarity factor (f2) obtained for batches 7 to 15 fell in the range 50 – 100 meaning the drug release profile of the batches was similar to the reference drug. Batches 7 to 13 and 15 had difference factors in the range 0 – 15 signifying a minor difference in the dissolution profile of those batches and the reference drug. From the results obtained, the gums and HPMC used individually could not sufficiently produce sustained release so must be combined in various ratios for effective sustained release to be achieved.
A Thesis submitted to the School of Graduate Studies, Kwame Nkrumah University of Science and Technology, Kumasi, in partial fulfilment of the requirements for the Degree of Master of Philosophy in Pharmaceutics, April-2012