本文選題：鹽酸多奈哌齊　切入點(diǎn)：分散片　出處：《天津醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:由于多奈哌齊片劑中輔料的選用不同,其崩解度、溶出度也不同。本課題重點(diǎn)優(yōu)化篩選了處方工藝。設(shè)計(jì)合理的各種輔料比例,提高鹽酸多奈哌齊的生物利用度。方法:首先,最優(yōu)處方的篩選。參考大量相關(guān)文獻(xiàn),篩選科學(xué)合理制備方法,運(yùn)用單因素考察,大致確定各種輔料的用法用量,應(yīng)用正交試驗(yàn)設(shè)計(jì)法,對鹽酸多奈哌齊分散片復(fù)方制劑進(jìn)行篩選并反復(fù)試驗(yàn)對鹽酸多奈哌齊分散片制作工藝過程進(jìn)行優(yōu)化,特別是對鹽酸多奈哌齊分散片中主要應(yīng)用的幾種輔料的大約加入量多次進(jìn)行摸索性試驗(yàn),根據(jù)主藥與輔料之間的合理應(yīng)用比例、分散時(shí)限、累積溶出百分率和含量均勻度等作為考察指標(biāo),多方面進(jìn)行綜合評價(jià),以市售口崩片為參考標(biāo)準(zhǔn),反復(fù)試驗(yàn)最終篩選出自制制劑的最優(yōu)處方。本制劑片面光潔美觀,分散均勻性、體外溶出經(jīng)都符合標(biāo)準(zhǔn)。處方設(shè)計(jì):鹽酸多奈哌齊原料藥5mg,微晶纖維素(MCC)45mg,交聯(lián)聚維酮(PVPP)9 mg,甘露醇(Mannitosel)60mg乳糖(Lactose)20 mg。以315 nm作為檢測波長,發(fā)現(xiàn)主藥色譜峰在經(jīng)過多次實(shí)驗(yàn)后其峰形較好,并且經(jīng)過多次實(shí)驗(yàn)后其重現(xiàn)性好,經(jīng)過多次實(shí)驗(yàn)后證明其輔料無干擾,所以選擇315 nm,最終作為最佳檢測波長來檢驗(yàn)多奈哌齊;以甲醇-水-三氟乙酸系統(tǒng)(V(甲醇):V(水):V(三氟乙酸)=75:25:0.2)為流動(dòng)相時(shí)。質(zhì)量控制是對鹽酸多奈哌齊分散片進(jìn)行的重要檢測步驟。對高效液相色譜法條件反復(fù)摸索、反復(fù)試驗(yàn),確保準(zhǔn)確、靈敏、操作簡便、易行,并對鹽酸多奈哌齊分散片自制制劑進(jìn)行質(zhì)量控制。最后,對鹽酸多奈哌齊分散片進(jìn)行穩(wěn)定性考察。通過幾種輔料的用量多少制定出最優(yōu)工藝和最優(yōu)處方,分別進(jìn)行影響因素試驗(yàn)包括光照實(shí)驗(yàn)、高濕試驗(yàn)以及高溫試驗(yàn),加速試驗(yàn)包括0、1、2、3、6個(gè)月考查,和長期試驗(yàn)包括0、3、6個(gè)月考查,為處方設(shè)計(jì)的合理性、為處方設(shè)計(jì)的科學(xué)、為鹽酸多奈哌齊分散片制作工藝的可行性、自制制劑的質(zhì)量控制、方便于包裝運(yùn)輸、貯存條件的科學(xué)化選擇等提供必要的資料。以上的研究方案作為對鹽酸多奈哌齊分散片自制制劑來講,為評價(jià)新藥的高標(biāo)準(zhǔn)質(zhì)量和指導(dǎo)臨床合理應(yīng)用鹽酸多奈哌齊分散片提供科學(xué)的合理的嚴(yán)謹(jǐn)?shù)囊罁?jù)。前期的摸索試驗(yàn)進(jìn)行了許多次,也充分證實(shí)了本試驗(yàn)具有可操作性和可行性,實(shí)驗(yàn)過程中僅需要常規(guī)實(shí)驗(yàn)室中的一般儀器,適合于普通實(shí)驗(yàn)室和臨床監(jiān)測應(yīng)用。結(jié)果:通過反復(fù)實(shí)驗(yàn)確定了輔料的用量比例,鹽酸多奈哌齊分散片處方中,應(yīng)用的各種輔料經(jīng)過反復(fù)試驗(yàn)在用量上依次為MCC30%,PVPP6%,甘露醇25%,乳糖15%。為了降低成本,加入了價(jià)格低廉的蛋白糖。本文在篩選處方時(shí)采用了單因素試驗(yàn)考察,通過考察分散均勻性、含量均勻度、累積溶出百分率等評價(jià)指標(biāo),結(jié)合試驗(yàn)設(shè)計(jì)方法,系統(tǒng)地全面地分析了重點(diǎn)考察因素,使得試驗(yàn)結(jié)果更為可靠。優(yōu)化出了鹽酸多奈哌齊分散片的最優(yōu)處方工藝。同時(shí)為鹽酸多奈哌齊分散片建立了準(zhǔn)確、可靠的質(zhì)量控制方法。建立了自制片劑含量測定方法。試驗(yàn)表明,鹽酸多奈哌齊在10.18μg/ml~122.01μg/ml的濃度范圍內(nèi)鹽酸多奈哌齊主峰峰形在對稱性方面很好,多奈哌齊分散片中的輔料對主藥測定基本沒有干擾。線性良好,準(zhǔn)確度高,精密度良好。該測定方法準(zhǔn)確,專屬性高,能夠有效地測定樣品的含量,簡便易行。通過影響因素試驗(yàn)的考察,該制劑應(yīng)存放在陰涼干燥處;6個(gè)月的長期試驗(yàn)比較短,在這期間內(nèi),制劑的各項(xiàng)重點(diǎn)考察指標(biāo)均符合要求,基本穩(wěn)定。需進(jìn)一步試驗(yàn)來確定有效期。結(jié)論:以鹽酸多奈哌齊為模型藥物制備鹽酸多奈哌齊分散片劑,篩選合適的處方工藝,建立了可靠的質(zhì)量控制方法,并對其進(jìn)行穩(wěn)定性考察,完成了片劑研制的基本工作。本文在篩選處方時(shí)采用了單因素試驗(yàn)考察,通過考察分散均勻性藥典二部要求全部通過2號篩、含量均勻度符合藥典二部規(guī)定、累積溶出百分率15 min時(shí)基本釋放完全,和評價(jià)指標(biāo)包括有關(guān)物質(zhì)的增長等,根據(jù)試驗(yàn)設(shè)計(jì)方法,全面分析了重點(diǎn)考察因素包括高溫高濕光照對多奈哌齊主藥及其幾種輔料的試驗(yàn)結(jié)果的影響,優(yōu)化出了鹽酸多奈哌齊分散片的最優(yōu)處方工藝。
[Abstract]:Objective: because of the use of donepezil in tablets of different materials, the disintegration and dissolution are also different. This paper optimize the prescription process. Reasonable design of various materials proportion, improve the bioavailability of donepezil hydrochloride. Methods: firstly, optimize the formulation. A large number of relevant references, select scientific and rational preparation methods using single factor test, roughly determine dosage of various excipients, using orthogonal design method, screening and manufacturing process of the Donepezil Hydrochloride Dispersible Tablets optimization trial of Donepezil Hydrochloride Dispersible Tablets compound, especially several materials on Application of Donepezil Hydrochloride Dispersible Tablets in the main content about several exploratory experiments, according to the main drug and excipients the reasonable utilization ratio, dispersion time, cumulative dissolution percentage and content uniformity as reference Observation index, comprehensive evaluation of many aspects, with a commercially available oral disintegrating tablets as the reference standard, repeated tests screened the optimal prescription preparation. The preparation of one-sided clean and beautiful, dispersion, after all meet the standard in vitro dissolution. Prescription design: donepezil hydrochloride raw medicine 5mg, microcrystalline cellulose (MCC) 45mg. Polyvinylpolypyrrolidone (PVPP) 9 mg (Mannitosel) 60mg, mannitol, lactose (Lactose) 20 mg. to 315 nm as the detection wavelength, found the main drug peaks after a number of experiments the good shape, and after repeated experiments after its good reproducibility, after many experiments that the materials without interference, so the choice of 315 nm, the final as the best detection wavelength to test donepezil; methanol - water - acetic acid system three fluorine (V (methanol): V (water): V (three trifluoroacetic acid) =75:25:0.2) as the mobile phase. The quality control is very important for the inspection of Donepezil Hydrochloride Dispersible Tablets The step of measuring. The HPLC conditions of repeated exploration, repeated testing, ensure accurate, sensitive, simple, easy, and Donepezil Hydrochloride Dispersible Tablets made preparations for quality control. Finally, the stability study was carried out on Donepezil Hydrochloride Dispersible Tablets. Through several accessories amount to develop the optimal process and the optimal prescription, respectively, including light influencing factor test according to the experiment, high humidity test, high temperature test, accelerated test including 0,1,2,3,6 months test and long-term test including 0,3,6 months test for rationality of prescription design, prescription design science, feasibility for Donepezil Hydrochloride Dispersible Tablets production process, quality control preparation, convenient for packaging and transportation, to provide the necessary data storage conditions scientific selection. Research scheme above as on Donepezil Hydrochloride Dispersible Tablets made preparations for, Provide a high standard of quality evaluation of new drugs and guide the reasonable clinical application of Donepezil Hydrochloride Dispersible Tablets's reasonable and rigorous basis. Experiments conducted many early, also confirmed that the test has the maneuverability and feasibility, the experimental process requires only routine laboratory instruments, suitable for general laboratory and clinical application of monitoring results: ratio of materials was determined by repeated experiments, Donepezil Hydrochloride Dispersible Tablets prescription, various materials used after repeated tests in the amount of the order of MCC30%, PVPP6%, 25% mannitol, lactose 15%. in order to reduce the cost of adding cheap protein sugar. Based on the prescription by screening single factor test, uniform through the investigation of dispersion, content uniformity, dissolution percentage, evaluation index, combined with the experimental design method, systematic and comprehensive Analysis of key factors, make the test results more reliable. The optimization of the optimal prescription and technology of Donepezil Hydrochloride Dispersible Tablets. At the same time for Donepezil Hydrochloride Dispersible Tablets to establish an accurate, reliable quality control method. To establish a method for the determination of self-made tablets. The test showed that in the concentration range of donepezil hydrochloride 10.18 g/ml~122.01 g/ml peak peak is in donepezil good in symmetry, in the piece of excipients on the determination of principal agents don't interfere with donepezil dispersion. Good linearity, high accuracy and good precision. The determination method is accurate and specific. It can effectively determine the sample content, simple and easy. By studying the influence factors test, the preparation should be stored in a cool and dry place; the long-term test of 6 months is relatively short, in this period, the emphasis on the preparation of indicators are in line with the requirements of the basic stability. Further tests to determine the validity of the model. Conclusion: the drug preparation of donepezil hydrochloride dispersible tablet with donepezil hydrochloride, prescription was selected appropriate, establish the quality control method is reliable, and the stability study was carried out on the completion of the basic work in this article. The preparations were used to screen prescription were studied through single factor test. All through the No. 2 sieve through the investigation of dispersion of the Pharmacopoeia two, the content uniformity in conformity with the provisions of Pharmacopoeia two, the cumulative dissolution percentage of 15 min totally released, and the evaluation index including the material growth, according to the experimental design method, a comprehensive analysis of the impact of key factors including the main test results of donepezil the medicine and some materials of high temperature and high Shiguang according to the optimization, the optimal formulation of Donepezil Hydrochloride Dispersible Tablets.

【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R943

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 羅曉茹;徐江;沈娟;李杉;劉俊;;不同廠家鹽酸多奈哌齊片體外溶出曲線比較[J];解放軍藥學(xué)學(xué)報(bào);2015年06期

2 李明;;鹽酸多奈哌齊在老年癡呆治療中的應(yīng)用研究[J];中國現(xiàn)代藥物應(yīng)用;2015年21期

3 王玉嬌;;分散片的研究進(jìn)展[J];北方藥學(xué);2015年11期

4 曾紀(jì)榮;;阿爾茨海默病藥物治療研究進(jìn)展[J];中國老年學(xué)雜志;2015年20期

5 李林;;中國阿爾茨海默病研究進(jìn)展[J];中國藥理學(xué)與毒理學(xué)雜志;2015年05期

6 閆文學(xué);;多奈哌齊聯(lián)合腦蛋白水解物治療血管性癡呆的效果分析[J];中國實(shí)用神經(jīng)疾病雜志;2015年19期

7 朱強(qiáng);鄧藍(lán)進(jìn);陳永建;鄭強(qiáng);柯瀟;;鹽酸多奈哌齊口崩片的溶出曲線相似性研究[J];中南藥學(xué);2015年05期

8 劉小均;羅軍波;李培海;鄭強(qiáng);柯瀟;;RP-HPLC加校正因子的主成分自身對照法測定鹽酸多奈哌齊口腔崩解片中有關(guān)物質(zhì)的含量[J];中國藥房;2015年12期

9 張軍霞;劉世國;黃勁松;岑千紅;;血漿和腦脊液中A_(42)的檢測在阿爾茨海默病診斷中的意義[J];中國實(shí)驗(yàn)診斷學(xué);2015年04期

10 涂紅梅;;老年癡呆應(yīng)用鹽酸多奈哌齊治療的臨床分析[J];中外醫(yī)學(xué)研究;2015年09期

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