| المستخلص: |
The aim of this work is to formulate and evaluate oro-dispersible tablets contains 500 mg metformin and 50 mg vildagliptin. A good method of analysis is needed for the assay and quantitation of both drugs in the proposed dosage form. A successful, simple, valid method of analysis for simultaneous determination of metformin and vildagliptin was developed using HPLC with UV detector. Acetonitrile-phosphate buffer pH 3 was used as a mobile phase and a successful separation and quantification was achieved with a retention time of 2.7 min for metformin and 5.1 min for vildagliptin. Linearity, precision, recovery and robustness were all tested according to the ICH guideline of pharmaceutical analysis. Four formulas were prepared, F1, F2 and F3 used three types of disintegrants, cross povidone, sodium starch glycolate and cross linked alginic acid respectively in concentration 5% of total weight of formula. Avicel and mannitol were used as diluents beside a flavor, a sweetener, a glidant and a lubricant in fixed amounts to achieve target weight of 1000 mg/tablet. Other formula (F4) was prepared using cross povidone as disintegrant but with different ratio of avicel-mannitol to investigate effect of avicel concentration on the parameters of evaluation. Powder mix of each formula was tested for flowability and compressibility. Then, tablets were compressed by direct compression method and evaluated according to the USP specifications of Oro-dispersible tablets. Results showed that the validation parameters of the proposed method of analysis were all within the limits of the ICH guideline. For both drugs, linearity achieved was very high (R2= 0.9999). Inter and intra -day precision was measured by percent relative standard deviation and was less than 2% for all tests. Recovery achieved for both drugs from all formulas was ranged from 98-102% with percent coefficient variation less than 1.5, and robustness of the method in different conditions related to the mobile phase, pH and column gave accuracy between 96-102%. The prepared powder mixtures of the four formulas showed good flow properties with angle of repose 34-37° and Carr’s Index 11-13.5 with free-flowing characteristics. F1 showed the shortest wetting time (20 seconds) and disintegration time (22 seconds) which satisfies both the USP and EMA specifications. Evaluation of all formulas showed an effect of type of disintegrant and diluent on wetting and disintegration times, where cross povidone gave the shortest time (20 seconds) while crossed linked alginic acid gave the longest (65 seconds). Also, decrease concentration of avicel resulted in increase in disintegration time (from 20 -35 seconds). Dissolution test of F1 in pH 1.2 and 6.8 showed very fast dissolution of both drugs where more than 85% of both drugs were released in less than 10 minutes. As a conclusion, the formulation design of metformin 500 mg - vildagliptin 50 mg was successful as Orodispersible tablets and the developed method of analysis was valid to be used in assay and quantitation of both drugs in the prepared tablets.
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