盐酸多奈哌齐分散片的研究

发布时间：2018-04-06 21:11

本文选题：盐酸多奈哌齐　切入点：分散片　出处：《天津医科大学》2017年硕士论文

【摘要】：目的:由于多奈哌齐片剂中辅料的选用不同,其崩解度、溶出度也不同。本课题重点优化筛选了处方工艺。设计合理的各种辅料比例,提高盐酸多奈哌齐的生物利用度。方法:首先,最优处方的筛选。参考大量相关文献,筛选科学合理制备方法,运用单因素考察,大致确定各种辅料的用法用量,应用正交试验设计法,对盐酸多奈哌齐分散片复方制剂进行筛选并反复试验对盐酸多奈哌齐分散片制作工艺过程进行优化,特别是对盐酸多奈哌齐分散片中主要应用的几种辅料的大约加入量多次进行摸索性试验,根据主药与辅料之间的合理应用比例、分散时限、累积溶出百分率和含量均匀度等作为考察指标,多方面进行综合评价,以市售口崩片为参考标准,反复试验最终筛选出自制制剂的最优处方。本制剂片面光洁美观,分散均匀性、体外溶出经都符合标准。处方设计:盐酸多奈哌齐原料药5mg,微晶纤维素(MCC)45mg,交联聚维酮(PVPP)9 mg,甘露醇(Mannitosel)60mg乳糖(Lactose)20 mg。以315 nm作为检测波长,发现主药色谱峰在经过多次实验后其峰形较好,并且经过多次实验后其重现性好,经过多次实验后证明其辅料无干扰,所以选择315 nm,最终作为最佳检测波长来检验多奈哌齐;以甲醇-水-三氟乙酸系统(V(甲醇):V(水):V(三氟乙酸)=75:25:0.2)为流动相时。质量控制是对盐酸多奈哌齐分散片进行的重要检测步骤。对高效液相色谱法条件反复摸索、反复试验,确保准确、灵敏、操作简便、易行,并对盐酸多奈哌齐分散片自制制剂进行质量控制。最后,对盐酸多奈哌齐分散片进行稳定性考察。通过几种辅料的用量多少制定出最优工艺和最优处方,分别进行影响因素试验包括光照实验、高湿试验以及高温试验,加速试验包括0、1、2、3、6个月考查,和长期试验包括0、3、6个月考查,为处方设计的合理性、为处方设计的科学、为盐酸多奈哌齐分散片制作工艺的可行性、自制制剂的质量控制、方便于包装运输、贮存条件的科学化选择等提供必要的资料。以上的研究方案作为对盐酸多奈哌齐分散片自制制剂来讲,为评价新药的高标准质量和指导临床合理应用盐酸多奈哌齐分散片提供科学的合理的严谨的依据。前期的摸索试验进行了许多次,也充分证实了本试验具有可操作性和可行性,实验过程中仅需要常规实验室中的一般仪器,适合于普通实验室和临床监测应用。结果:通过反复实验确定了辅料的用量比例,盐酸多奈哌齐分散片处方中,应用的各种辅料经过反复试验在用量上依次为MCC30%,PVPP6%,甘露醇25%,乳糖15%。为了降低成本,加入了价格低廉的蛋白糖。本文在筛选处方时采用了单因素试验考察,通过考察分散均匀性、含量均匀度、累积溶出百分率等评价指标,结合试验设计方法,系统地全面地分析了重点考察因素,使得试验结果更为可靠。优化出了盐酸多奈哌齐分散片的最优处方工艺。同时为盐酸多奈哌齐分散片建立了准确、可靠的质量控制方法。建立了自制片剂含量测定方法。试验表明,盐酸多奈哌齐在10.18μg/ml~122.01μg/ml的浓度范围内盐酸多奈哌齐主峰峰形在对称性方面很好,多奈哌齐分散片中的辅料对主药测定基本没有干扰。线性良好,准确度高,精密度良好。该测定方法准确,专属性高,能够有效地测定样品的含量,简便易行。通过影响因素试验的考察,该制剂应存放在阴凉干燥处;6个月的长期试验比较短,在这期间内,制剂的各项重点考察指标均符合要求,基本稳定。需进一步试验来确定有效期。结论:以盐酸多奈哌齐为模型药物制备盐酸多奈哌齐分散片剂,筛选合适的处方工艺,建立了可靠的质量控制方法,并对其进行稳定性考察,完成了片剂研制的基本工作。本文在筛选处方时采用了单因素试验考察,通过考察分散均匀性药典二部要求全部通过2号筛、含量均匀度符合药典二部规定、累积溶出百分率15 min时基本释放完全,和评价指标包括有关物质的增长等,根据试验设计方法,全面分析了重点考察因素包括高温高湿光照对多奈哌齐主药及其几种辅料的试验结果的影响,优化出了盐酸多奈哌齐分散片的最优处方工艺。
[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.

【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R943

【参考文献】