| Summary: | 碩士 === 國立臺灣大學 === 藥學研究所 === 87 === Cisapride is a gastrokinetic drug whose activity is considered to enhance the physiological release of acetylcholine at the myenteric plexus. It is reported to be an agonist at serotonin-4 (5-HT4) receptor. It is a synthetic piperidinyl benzamide, and practically insoluble in water, sparingly soluble in methanol. Due to its lipophilic property, the dissolution of cisapride tablets is more difficult than hydrophilic drugs. In this work the designed formulations of cisapride tablets were studied.Factorial design is widely used in experiment involving several factors where it is necessary to study the join effect of the factors on a response. The whole experiment is based on the 2^3 factorial experimental design. Three factors were discussed from this design, and found which one is the critical factor. The three independent variables were citric acid, PEG, and particle size of cisapride, and eight combined formulations were designed.The process to make tablets was direct press method because it was simple, convenient, and time saving. The content uniformity analysis by HPLC was used to assure each tablet's content. The physicochemical property of these formulations was determined by using differential scanning calorimetry (DSC).The dissolution was based on the USP paddle method. The experiments were processed on two dissolution media, pH 7.4 phosphate buffer and 0.1N HCl solution with 0.5% SDS. The results of dissolution were calculated by the weight means of each formulation. The calculated dissolution curves were fitted by Weibull equation to get two parameters, k (pseudo first-order rate constant) and β (the sigmoid degree of the curve). The responses were evaluated by these two parameters and the yield. The results after the statistical analysis were that β was impacted by all three factors, and k was affected by PEG and particle size, the yield was also militated by PEG and particle size in the pH 7.4 phosphate buffer. In 0.1N HCl solution, β was not explained by any factors, k was determined only by particle size, and the yield was effected by PEG and particle size.
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