本文選題：富馬酸喹硫平緩釋片 + Plackett-Burman設(shè)計(jì)��； 參考：《南華大學(xué)》2014年碩士論文

【摘要】：目的： 建立富馬酸喹硫平緩釋片體外釋放及檢測(cè)累計(jì)釋放度方法、喹硫平含量及有關(guān)物質(zhì)測(cè)定方法；通過體外評(píng)價(jià)及考察本品在不同條件下的穩(wěn)定性，，確定富馬酸喹硫平緩釋片處方及制備工藝。 方法： 1）富馬酸喹硫平緩釋片釋放裝置采用USP I法（籃法），檸檬酸鹽為釋放介質(zhì)，轉(zhuǎn)速100r/min，采用UV法于288nm處測(cè)定喹硫平吸光度，計(jì)算累計(jì)釋放度，與市售Seroquel XR做相似性判斷，作為體外評(píng)價(jià)方法。 2）喹硫平及有關(guān)物質(zhì)的含量測(cè)定方法：采用HPLC法，用XDB-C8為色譜柱；以乙腈-甲醇-0.02mol/L磷酸氫二銨溶液（7:54:39）為流動(dòng)相；檢測(cè)波長為230nm；流速1.0mL/min；進(jìn)樣量20μL。 3）以累積釋放度的綜合評(píng)分作為響應(yīng)值，運(yùn)用Plackett-Burman設(shè)計(jì)篩選出顯著性影響因素，并將其作為自變量，用CCD-效應(yīng)面法對(duì)處方工藝進(jìn)行優(yōu)化。 結(jié)果： 1）Plackett-Burman設(shè)計(jì)聯(lián)合CCD-效應(yīng)面法篩選預(yù)測(cè)最優(yōu)處方為：38.33%富馬酸喹硫平、11.29%HPMC K4M、17.20%PVP K90、8.00%枸櫞酸鈉、8.00%MCC、15.14%乳糖、2.00%硬脂酸鎂。 2）供試片與Seroquel XR在去離子水、 pH1.2鹽酸溶液、 pH6.8磷酸鹽緩沖液、檸檬酸鹽溶液中的相似因子分別為74、84、82、69，相似性判斷為良好。 3）在影響因素試驗(yàn)和加速試驗(yàn)中采用HPLC測(cè)得富馬酸喹硫平緩釋片的有關(guān)物質(zhì)的含量：?jiǎn)蝹�(gè)雜質(zhì)小于0.15%，未知雜質(zhì)單個(gè)雜質(zhì)小于0.15%，總雜質(zhì)小于0.4%，符合標(biāo)準(zhǔn)要求。 結(jié)論： 1)富馬酸喹硫平緩釋片體外釋放及檢測(cè)累計(jì)釋放度方法、喹硫平及有關(guān)物質(zhì)測(cè)定方法具有可行性。 2) Plackett-Burman設(shè)計(jì)聯(lián)合CCD-效應(yīng)面法得到的預(yù)測(cè)最優(yōu)處方工藝，體外評(píng)價(jià)結(jié)果與市售Seroquel XR釋放行為一致，有關(guān)物質(zhì)檢測(cè)項(xiàng)符合標(biāo)準(zhǔn)，可確定為最優(yōu)處方工藝。
[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.
【學(xué)位授予單位】：南華大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R944

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 曾凡新,傅潔民,董志;非典型抗精神病藥的受體藥理學(xué)研究進(jìn)展[J];中國臨床藥理學(xué)雜志;2003年05期

2 胡華;王立偉;;喹硫平治療心境障礙的作用機(jī)制[J];上海精神醫(yī)學(xué);2008年01期

3 楊勇超;馬中華;郜曉輝;張淑芳;吳滔;劉文靜;;氯氮平和奎硫平對(duì)血清催乳素的影響[J];臨床精神醫(yī)學(xué)雜志;2006年04期

4 勾蕾;陶學(xué)良;劉麗蓉;張文斌;;奎硫平治療抑郁癥的增效作用[J];臨床精神醫(yī)學(xué)雜志;2010年02期

5 劉艷妮;高麗;蔣海松;丁黎;;HPLC法測(cè)定富馬酸喹硫平緩釋片中喹硫平氮氧化物及其它有關(guān)物質(zhì)[J];黑龍江醫(yī)藥;2012年03期

6 馬培奇;;美FDA批準(zhǔn)富馬酸喹硫平緩釋片Seroquel XR用作嚴(yán)重抑郁癥附加治療藥物[J];上海醫(yī)藥;2010年03期

7 李坤艷;李煥德;;中國精神分裂癥患者多劑量喹硫平及其代謝產(chǎn)物的藥代動(dòng)力學(xué)[J];中國藥物應(yīng)用與監(jiān)測(cè);2006年03期

8 耿立堅(jiān);李性天;李湘沙;;新型抗精神病藥臨床再評(píng)價(jià)[J];中國藥房;2006年07期

9 張明廉;袁國楨;姚建軍;張?jiān)票?唐琳;吳越;周德祥;董小惠;劉雨生;;精神分裂癥患者血清催乳素和生長激素水平與奎硫平、氟哌啶醇治療關(guān)系的對(duì)照研究[J];中國神經(jīng)精神疾病雜志;2005年06期

10 譚云;邵江勇;趙敏;吳范宏;;喹硫平的合成改進(jìn)研究[J];中國新藥雜志;2007年11期

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