The development of phenytoin sodium controlled release tablet
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Abstract
Introduction: Phenytoin is an anticonvulsant drug with narrow therapeutic range. It is a weak acid which makes it practically insoluble in water. Phenytoin sodium formulation is developed in order to increase the solubility. Taking phenytoin sodium orally or in acid conditions will result in converting phenytoin sodium to phenytoin free acid and will cause low absorption and fuctuation of plasma drug concentration. Objective: To develop mini-tablet phenytoin sodium multiple unit dosage forms. The phenytoin formulation was designed to release in the stomach, small intestine and large intestine. The pH adjusted material was added to the tablet to control the pH of the diffusion layer around the tablet higher than the pKa (8.3). This would increase the solubility of phenytoin sodium in the stomach and intestine. Materials and methods: Development of phenytoin sodium mini-tablets was performed. Each tablet contained 25 mg phenytoin sodium, fller, lubricant, and sodium bicarbonate in various concentrations as the pH adjusting agent in the tablet to protect converting of phenytoin sodium to phenytoin free acid and improve solubility in intestinal conditions. Some of the mini-tablets were coated with Coteric® L 100 to control drug release in small intestine and some were coated with Polycoat® S 100 to control drug release in large intestine. Mini-tablets were evaluated by USP and BP guidelines such as hardness, friability, weight variation, disintegration time, content uniformity, and dissolution testing. The mini-tablets were flled in capsules with ratio of uncoated: Coteric®L 100 coated: Polycoat®S 100 coated 1: 2: 1 and dissolution tested in 0.1 N HCl for 2 hrs, pH 6.8 phosphate buffer for 3 hrs, pH 7.4 phosphate buffer for 2 hrs. Results: The mini-tablets in formulas 1, 2, and 3 had an average weight 50.69, 50.94, and 50.98 mg respectively. The percentages of friability were 0.62, 0.28, and 0.57 respectively. The content uniformities were 97.30±1.66, 97.33±1.79, and 97.84±3.49 respectively. Drug releases from dissolution testing in 0.1 N HCl were 25.54, 23.41, and 22.01%, in pH 6.8 phosphate buffer were 71.57, 50.15, and 41.90%, and in pH 7.4 phosphate buffer were 91.55, 67.26, and 55.02% respectively. Conclusion: The product can release the active ingredient at acid, pH 6.8 phosphate buffer and pH 7.4 phosphate buffer as designed. However the higher the sodium bicarbonate level, the lower the release of active ingredient.
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