| Indomethacin belongs to the non-steroidal anti-inflammatory drugs(NSAID), which can effectively inhibit cycloxygenase(COX) and have the effects of analgesic as well as antipyretic. It has been widely used in clinical since it was marketed in 1960 s and was considered to be more promising than aspirin and paracetamol. However, Indomethacin is one of the BCS II drugs which is poorly water soluble. The conventional formulation of Indomethacin show low bioavailability, which limits its clinical application. Hence, it is possible to develop a new kind of formulation for Indomethacin.Magnetic mesoporous carbon have huge potential in drug delivery system(DDS) owing to its uniform pore diameter between 2-50 nm, good biocompatibility, stable structure, large surface area and pore volumn. It can improve the solubility of drug by enhancing the dispersibility and decreasing the crystallinity of drug.In this research, the magnetic mesoporous carbon(MMC) was prepared by simple one step method. The solubility and dissolution rate of the model drug Indomethacin(INC) loaded into the pore channel of MMC were greatly improved, which is in favour of enhancing the bioavailability, reducing the dosage and weakening the side effects of drug.Main contents of the paper are as follows:1. The UV analytical method of INC and its formulation products has been established。The result reveals that the INC was stable within 24 h in room temperature. The recovery rate of INC was nearly 100%, which means that the carrier has no effects on the measurement of INC. The solubility of INC in DI water, pH 6.8 and pH 1.2 buffer solution were 23.28、849.07 and 0.26 μg·mL-1,respectively, The pH 6.8 was picked to be the dissolution media because it meets the requirements of sink condition.2. The synthesis technology research of MMC. The surface area and pore diameter were set as the main evaluation indexes and the optimal prescription for process was investigated by single factor experiment, the result are as follows: polymer temperature was 80℃, calcinations temperature was 850℃, the concentration of Fe(NO3)3·9H2O was 0.05 mg/mL, the ratio of sucross/siica was 2/1. The morphology of the resulting MMC was spheres and the average partical size was 17μm. The SBET, VP and DP of MMC were 1213 m2/g, 3.15 m3/g and 6.46 nm, respectively.3. The effects of the drug/carrier ratio and the drug loading time on the synthesis of INC/MMC were investigated. The optimal drug loading process were as follows: drug/carrier ratio was 1/1, the stirring time is 3h. The loading degree of INC/MMC is 32.87% and the drug in the MMC pore channel was amorphous form. The stability test reveals that the INC/MMC was stable in 6 months.4. The equilibrium solubility of INC/MMC in DI water was investigated and the value is 109.44 μg·mL-1, which is nearly 5 times than the pure INC. The dissolution test in pH 6.8 reveals that the dissolution rate of INC/MMC was remarkable improved and reached 84.2% in 15 min. The dissolution process of INC/MMC was fitted by the First-order model, the coefficient association is 0.99 and the dissolution rate in infinity time is 92.2%, the dissolution rate constant is 0.22. The similarity factor for the dissolution processes between two batches of INC/MMC is 65.8, which means good reproducibility.5. The MTT test was used to research the cytotoxicity of MMC. The results shows that the MMC has no cytotoxicity between the concentration of 0.1~1000 μg/mL, which means good biocompatibility. |
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