富马酸喹硫平缓释片的处方优化与质量分析

发布时间：2018-05-07 15:31

本文选题：富马酸喹硫平缓释片 + Plackett-Burman设计　；参考：《南华大学》2014年硕士论文

【摘要】：目的：建立富马酸喹硫平缓释片体外释放及检测累计释放度方法、喹硫平含量及有关物质测定方法；通过体外评价及考察本品在不同条件下的稳定性，，确定富马酸喹硫平缓释片处方及制备工艺。方法： 1）富马酸喹硫平缓释片释放装置采用USP I法（篮法），柠檬酸盐为释放介质，转速100r/min，采用UV法于288nm处测定喹硫平吸光度，计算累计释放度，与市售Seroquel XR做相似性判断，作为体外评价方法。 2）喹硫平及有关物质的含量测定方法：采用HPLC法，用XDB-C8为色谱柱；以乙腈-甲醇-0.02mol/L磷酸氢二铵溶液（7:54:39）为流动相；检测波长为230nm；流速1.0mL/min；进样量20μL。 3）以累积释放度的综合评分作为响应值，运用Plackett-Burman设计筛选出显著性影响因素，并将其作为自变量，用CCD-效应面法对处方工艺进行优化。结果： 1）Plackett-Burman设计联合CCD-效应面法筛选预测最优处方为：38.33%富马酸喹硫平、11.29%HPMC K4M、17.20%PVP K90、8.00%枸橼酸钠、8.00%MCC、15.14%乳糖、2.00%硬脂酸镁。 2）供试片与Seroquel XR在去离子水、 pH1.2盐酸溶液、 pH6.8磷酸盐缓冲液、柠檬酸盐溶液中的相似因子分别为74、84、82、69，相似性判断为良好。 3）在影响因素试验和加速试验中采用HPLC测得富马酸喹硫平缓释片的有关物质的含量：单个杂质小于0.15%，未知杂质单个杂质小于0.15%，总杂质小于0.4%，符合标准要求。结论： 1)富马酸喹硫平缓释片体外释放及检测累计释放度方法、喹硫平及有关物质测定方法具有可行性。 2) Plackett-Burman设计联合CCD-效应面法得到的预测最优处方工艺，体外评价结果与市售Seroquel XR释放行为一致，有关物质检测项符合标准，可确定为最优处方工艺。
[Abstract]:Objective: To establish a method for in vitro release and detection of cumulative release of quetiapine fumarate sustained-release tablets, to determine the content of quintiapine and its related substances, and to evaluate and investigate the stability of the tablets under different conditions. To determine the formulation and preparation process of quetiapine fumarate sustained-release tablets. Methods: 1) Quinthiapine fumarate sustained-release tablet was released by USP I method (basket method, citrate as release medium, rotational speed 100r / min, UV method was used to determine the absorbance of quinolipine at 288nm, the cumulative release degree was calculated, and the similarity judgement was made with Seroquel XR on the market. As an in vitro evaluation method. 2) determination of quetiapine and its related substances by HPLC method with XDB-C8 as chromatographic column, acetonitrile-methanol-0.02 mol / L diammonium hydrogen phosphate solution (7: 54: 39) as mobile phase, detection wavelength at 230 nm, flow rate at 1.0 mL / min, sample injection amount at 20 渭 L. 3) the comprehensive score of cumulative release was used as the response value, the significant influencing factors were screened by Plackett-Burman design, and the formulation process was optimized by CCD-effect surface method. Results: 1)Plackett-Burman design combined with CCD-effect surface method was used to screen and predict the optimal formulation: 1: 38.33% quetiapine fumarate 11.29% HPMC K4MN 17.20, PVP K90 8.00% sodium citrate 8.00MCC15.14% lactose and 2.00% magnesium stearate. 2) the similarity factors between the sample and Seroquel XR in deionized water, pH1.2 hydrochloric acid solution, pH6.8 phosphate buffer solution and citrate solution were 74n84O82N 69, respectively, and the similarity was good. 3) the content of the related substances in the sustained release tablets of quetiapine fumarate was determined by HPLC in the influence factor test and accelerated test: the single impurity was less than 0.15, the unknown impurity was less than 0.15 and the total impurity was less than 0.4, which met the standard requirement. Conclusion: 1) the method of in vitro release and detection of cumulative release of quetiapine fumarate sustained-release tablets and the method for determination of quetiapine and its related substances are feasible. 2) the Plackett-Burman design combined with CCD-effect surface method was used to predict the optimal prescription process. The results of in vitro evaluation were consistent with the release behavior of Seroquel XR on the market. The related substances met the standard and could be determined as the optimal prescription process.
【学位授予单位】：南华大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R944

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