Formulation and Optimization of Taste-masked Orodispersible Tablets of Styrene- Divinyl Benzene Copolymer Complexed Metoclopramide by Sublimation Technique

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Addis Ababa University


Metoclopramide (MCP) is used to treat gastroparesis, by stimulating stomach activity to empty the stomach. The matter that complicates oral administration of MCP is the fact that patients with gastroparesis often have symptoms such as vomiting and nausea as well as fullness and bloating, each of which can lead to patient discomfort with or unwillingness to swallow the available oral tablet and associated water. If vomiting takes place, the amount of MCP that remains in the stomach is unknown, and the result of treatment is even less predictable. This study provides a rapidly dissolving oral MCP formulation and administration of MCP for immediate release formulation to abate the rapid onset of gastroparesis. Conventional taste masking techniques such as use of sweeteners, amino acids, flavoring agent are often unsuccessful in masking the taste of highly bitter drugs since they are overpowered by the taste of the medicine. MCP is an intensely bitter drug; hence, if it is incorporated directly into an orodispersible tablet (ODT), the main objective behind formulation of such a dosage form will definitely become futile. Hence, ion exchange resin (IER) has been used as drug carrier to mask its taste after the drug is loaded into an IER by an exchanging reaction, with the formation of drug–resin complex. Screening experiments for parameters such as: drug to resin ratio, swelling time and stirring (complexation) time were optimized to 1:3, 30 min and 1 h, respectively, for maximum drug loading. The effect of temperature was found to be not significant on maximum amount of drug loading. During preparation of drug resin complex (resinate), the other variables were kept constant. The effect of formulation variables (concentration of ammonium bicarbonate as subliming agent, concentration of crospovidone as superdisintegrant and amount of microcrystalline cellulose (MCC)) and a process variable (compression force) on tablet hardness, disintegration time, and friability was optimized using 24 randomized full factorial design. Accordingly, the various models describing the relationship of the selected variables were obtained using Design-Expert software and the models were analyzed. The corresponding surface response and contour plots were also obtained and the optimum area was determined and, then validated. Simultaneous optimization of the responses gave the most desirable representative optimum formulation, within the common optimum region, with a disintegration time of 17.82 s, ix hardness of 75.49 N and friability 0.40% at ammonium carbonate 14.20%, crospovidone 6.14%, MCC 51.31% and compression force 10.15 KN. The validity of obtained optimal point was confirmed by the low magnitude of percent prediction error. With that a stable, taste-masked MCP ODTs, which is suitable for patients with gastroparesis was developed. The prepared optimized formulations were characterized for powder properties, tablets morphology, in vitro drug release behavior, taste-masking and stability. The study showed that a porous, taste-masked, and stable MCP ODTs with superior in-vitro drug release profile as compared to available marketed products, which is suitable for patients with gastroparesis was developed. Key words: metoclopramide, ion exchange resin, resinate, orally disintegrating tablets, taste-masking, sublimation technique, optimization, full factorial design



Metoclopramide; Ion exchange resin; Resinate; Orally disintegrating tablets,Taste-masking,Sublimation technique, optimization, full factorial design