發(fā)布時間：2018-04-06 21:11

  本文選題：鹽酸多奈哌齊　切入點：分散片　出處：《天津醫(yī)科大學》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。本課題重點優(yōu)化篩選了處方工藝。設計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。參考大量相關文獻,篩選科學合理制備方法,運用單因素考察,大致確定各種輔料的用法用量,應用正交試驗設計法,對鹽酸多奈哌齊分散片復方制劑進行篩選并反復試驗對鹽酸多奈哌齊分散片制作工藝過程進行優(yōu)化,特別是對鹽酸多奈哌齊分散片中主要應用的幾種輔料的大約加入量多次進行摸索性試驗,根據(jù)主藥與輔料之間的合理應用比例、分散時限、累積溶出百分率和含量均勻度等作為考察指標,多方面進行綜合評價,以市售口崩片為參考標準,反復試驗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)都符合標準。處方設計: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)過多次實驗后其峰形較好,并且經(jīng)過多次實驗后其重現(xiàn)性好,經(jīng)過多次實驗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)為流動相時。質(zhì)量控制是對鹽酸多奈哌齊分散片進行的重要檢測步驟。對高效液相色譜法條件反復摸索、反復試驗,確保準確、靈敏、操作簡便、易行,并對鹽酸多奈哌齊分散片自制制劑進行質(zhì)量控制。最后,對鹽酸多奈哌齊分散片進行穩(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,分別進行影響因素試驗包括光照實驗、高濕試驗以及高溫試驗,加速試驗包括0、1、2、3、6個月考查,和長期試驗包括0、3、6個月考查,為處方設計的合理性、為處方設計的科學、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、方便于包裝運輸、貯存條件的科學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,為評價新藥的高標準質(zhì)量和指導臨床合理應用鹽酸多奈哌齊分散片提供科學的合理的嚴謹?shù)囊罁?jù)。前期的摸索試驗進行了許多次,也充分證實了本試驗具有可操作性和可行性,實驗過程中僅需要常規(guī)實驗室中的一般儀器,適合于普通實驗室和臨床監(jiān)測應用。結(jié)果:通過反復實驗確定了輔料的用量比例,鹽酸多奈哌齊分散片處方中,應用的各種輔料經(jīng)過反復試驗在用量上依次為MCC30%,PVPP6%,甘露醇25%,乳糖15%。為了降低成本,加入了價格低廉的蛋白糖。本文在篩選處方時采用了單因素試驗考察,通過考察分散均勻性、含量均勻度、累積溶出百分率等評價指標,結(jié)合試驗設計方法,系統(tǒng)地全面地分析了重點考察因素,使得試驗結(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。同時為鹽酸多奈哌齊分散片建立了準確、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,準確度高,精密度良好。該測定方法準確,專屬性高,能夠有效地測定樣品的含量,簡便易行。通過影響因素試驗的考察,該制劑應存放在陰涼干燥處;6個月的長期試驗比較短,在這期間內(nèi),制劑的各項重點考察指標均符合要求,基本穩(wěn)定。需進一步試驗來確定有效期。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。本文在篩選處方時采用了單因素試驗考察,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時基本釋放完全,和評價指標包括有關物質(zhì)的增長等,根據(jù)試驗設計方法,全面分析了重點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.

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

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本文編號：1718920