| Obejective: Famotidine is a new H2-receptor antagonist and very effective in the treatment peptic ulcer and duodenum ulcer. Clinincal study shows that the dose of famotidine in the treatment is 40mg once in a day. But the administration makes the plasma concentration change enormously, which is not suitable in treatment. The main products are ordinary tablets, ordinary capsules and injections, the bioavailability is 45-50%. In order to solve problems mentioned, the sustained-release capsules were prepared by using HPMC as hydrophilic matrix to make release slow.Method: After reading scientific materials and the pre-preparation, the orthogonal experiment design L9(34) was used to select the preliminary formulation. On the basis of the preliminary prescription, the orthogonal experiment design L4(22) was used to select the best prescription. In the orthogonal experiment, the standard for judgement of in vitro release was accumulated release percent. The release behavior of sustained-release capsule was studied by oar method. The release mediumis 0.1M HCL, and temperature is 37+ 1C,samples were obtained 0.5, 1, 2, 4, 6, 8, 12, 18, 24h and quantitated at 266nm by Ultraviolet spectrophotometer. Three batches of sustained-release capsules were prepared and studied through release experiment to confirm the stability of formulation. The release data were analyzed by three model: Higuchi equation, zero order kinetics, first order kinetics. 8 rabbits were divided into 2 groups. One was given sustained-release capsules, another was given market tablets. Plasma samples were obtained at different time. A highly performance liquid chromatographic method was developed to determine famotidine concentration in rabbit's plasma.Result: The optimal formulation was founded by terms of orthogonal experiment: famotidine 40mg, HPMC 60mg, stearic acid 40mg, stearyl alcohol 50mg were mixed and heated at 80 C for 10 minutes . In the optimal formulation, HPMC was matrix, HPMC could swell in water and form hydrogel to control the release of famotidine ; the melting span of Stearic acid was 64-70 C, when melted at 80 C, it could make all ingredients into a whole, it also controled the release of famotidine; stearyl alcohol was auxiliary blocking agenta and able to regulate the release of famotidine. Three batches of sustained-release capsules were prepared arrording to theoptimal formulation and studied through release experiment. The release data were analyzed by three model: Higuchi equation, zero order kinetics, first order kinetics, the release property more conformed Higuchi equation. The correlation of the linear range was good between 3-25 u g/ml,C=32.278A℃0.0836, (r=0.9998). The recoverieswere: 98.66℃1.60%, 99.44℃0.19% , 99.53℃1.30%, respectively, RSD: 1.65%, 0.187%, 1.28%.The contents of three batches of sustained-release capsules were 96.69℃1.85%, 94.42℃2.20%, 98.25℃2.34%. The release time exceeded 12 hours. The result of pharmacokinetics in rabbit showed that sustained-release capsules and market tablets all conformed one-compartm -ent model. The result of t-test showed that there was obvious difference between their pharmacokinetic parame -ters.Conclusion: The result of release experiment in vitro and pharmacokinetic study in rabbits showed that sustained-release capsules possessed the obvious properities of sustained-release preparation in vitro and in vivo.
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