正交设计筛选头孢克肟直接压片的处方工艺

目的粉末直接压片法研究制备头孢克肟片.方法采用正交设计筛选处方工艺,选择出最优处方并验证,进行质量考察.结果样品的片重差异、溶出度、含量均符合质量标准.经加速稳定性试验考察,各项考察指标均符合质量标准.结论本研究制备头孢克肟片工艺简单,质量稳定,适用于工业化生产.     

头孢克洛片的研究

为了保护头孢克洛的稳定性,采用原料粉末直接压片法制备头孢克洛片,各项指标符合质量标准要求,10min时的溶出度>80%。     

头孢克洛片的研究

为了保护头孢克洛的稳定性，采用原料粉末直接压片法制备头孢克洛片，各项指标符合质量标准要求，10min时的溶出度＞80％。     

头孢克洛片的研究

为了保护头孢克洛的稳定性,采用原料粉末直接压片法制备头孢克洛片,各项指标符合质量标准要求,10min时的溶出度>80%。     

辛伐他汀片粉末的直接压片工艺

目的:建立辛伐他汀片粉末直接压片的新工艺.方法:使用新型的速释直接压片辅料,筛选出可压性和流动性均好的稀释剂,建立粉末直接压片的新工艺.经影响因素试验、加速试验及长期试验考察,检测辛伐他汀片的性状、溶出度、含量及有关物质.结果:粉末直接压片制备的辛伐他汀片稳定性良好.在各种考察条件下,样品的外观、含量、有关物质及溶出度均未发生明显变化,45 min时溶出度在95%以上.结论:辛伐他汀片剂质量稳定,粉末直接压片新工艺不会引起辛伐他汀降解.     

粉末直接压片法制备格列本脲片及稳定性考察

采用粉末直接压片工艺制备格列本脲片,以乳糖为助流剂,微晶纤维素为吸附剂,HPLC法检测含量及有关物质.加速稳定性试验表明,制品稳定性优于湿法制粒工艺所得产品.     

头孢克洛干混悬剂的稳定性研究

目的:考察头孢洛克干混悬剂的稳定性,预测其有效期,为药物保管和使用提供合理依据。方法:以制剂的性状、酸度、溶出度、有关物质和含量变化为稳定性考察指标,采用加速试验和长期试验方法,对头孢克洛干混悬剂的稳定性进行考察。结果:头孢克洛干混悬剂稳定性较好,在室温25℃,相对湿度(RH)60%的环境下保持性状的稳定,其在室温下有效期约2年。结论:头孢克洛干混悬剂的稳定性良好。     

头孢克肟片直压制备工艺的研究

目的：建立粉末直接压片法制备头孢克肟片的新工艺,防止生产过程中头孢克肟效价降低。方法：选用新型直接压片用辅料,利用粉末直接压片法制备其片剂,并以市售头孢克肟片为参比制剂,进行质量研究。结果：直接压片粉末具有良好的流动性和可压性,制得的头孢克肟片各项指标符合质量标准要求。结论：本研究不仅增加了头孢克肟的稳定性,提高了药物溶出度,而且简化了工艺过程,降低了生产成本,适合工业化生产。     

复方头孢克洛片制备及稳定性考察

目的 研究复方头孢克洛片的处方和制备工艺.方法 配制复方头孢克洛片,并制定质量标准,采用高效液相色谱法测定含量及进行稳定性考察.结果 以该处方工艺制成的片剂,质量可控,稳定性较好.结论 本品处方工艺成熟,质量可控,稳定性较好.     

水分活度对头孢克洛干混悬剂稳定性的影响

目的根据干混悬剂的制剂特点,探讨水分活度对头孢克洛干混悬剂稳定性的影响。方法通过高湿加速试验[温度(25±1)℃,相对湿度(75±1)%],考察头孢克洛干混悬剂水分含量、水分活度和杂质的变化。结果头孢克洛干混悬剂杂质总量的变化与水分活度的变化呈正相关,水分活度增长低的样品稳定性高。结论不同企业样品的处方差异可能是导致其水分活度和杂质变化存在差异的主要原因。     

氯氮平口腔崩解片的制备及质量控制

目的制备氯氮平口腔崩解片并探讨其质量控制。方法考察填充剂微晶纤维素、甘露醇及崩解剂交联羧甲基纤维素钠的用量,以外观、口感及体外崩解时间为指标,通过正交试验优化处方,采用直接压片法制备口腔崩解片,并对其崩解时间、溶出度、含量进行检测。结果氯氮平口腔崩解片在30s内可完全崩解,2min溶出达90％以上,含量符合规定。结论处方设计合理,制备工艺可行,产品质量可控。     

Effect of different acids on solid-state stability of an ester prodrug of a IIb/IIIa glycoprotein receptor antagonist.

DMP 754 is an ester prodrug of a fibrinogen glycoprotein IIb/IIIa receptor antagonist. The purpose of this study was to determine whether the addition of acids to blends containing DMP 754 and anhydrous lactose could improve the stability at 40 degrees C/75% relative humidity. DMP 754 drug substance was stable at this accelerated condition. Blending of DMP 754 with anhydrous lactose accelerated the hydrolysis of both the ester and the amidine groups. The pH of a saturated solution of lactose is approximately 6, whereas the pH of maximum solution stability for the drug substance is approximately 4. Acids were incorporated into the blend so that the microenvironment would be more acidic and afford improved drug stability. Addition of acids decreased the rate of hydrolysis of the amidine group and this effect was more pronounced with stronger acids. However, the more acidic ingredients led to more rapid hydrolysis of the ester group.     

An evaluation of microcrystalline cellulose and lactose excipients using an instrumented single station tablet press

The objective of this study was to evaluate the effects of microcrystalline cellulose of two particle sizes from two suppliers at two concentration levels, in combination with anhydrous lactose or Fast-Flo lactose on various properties of hydrochlorothiazide tablets. The powder blends before compression were evaluated for flow, density and compressibility. Tablets were compressed at three hardnesses and evaluated for friability, disintegration and hydrochlorothiazide dissolution. Powder blends containing Fast-Flo lactose exhibited a flow rate predicted to be sufficient for high-speed tableting whereas only when anhydrous lactose was used with the larger particle size microcrystalline cellulose was the same degree of flowability obtained. Density was affected by the concentration of microcrystalline cellulose. Fast-Flo lactose markedly increased density at the lower level of microcrystalline cellulose concentration. No difference was found in blend compressibility as a result of microcrystalline cellulose particle size or supplier source at medium to high tablet hardness levels, however, anhydrous lactose blends were more compressible than Fast-Flo lactose blends. At all hardness levels, tablets from all blends exhibited excellent friability. In most instances, tablet disintegration seemed to be more rapid when Fast-Flo lactose was present. Hydrochlorothiazide dissolution from all tablets easily met USP specifications. The microcrystalline cellulose from the two sources are interchangeable within particle size classification. Anhydrous lactose is more compressible than Fast-Flo lactose but Fast-Flo lactose is more flowable and its use results in more rapid drug dissolution at the higher microcrystalline cellulose levels.     

氯雷他定口崩片的制备及初步稳定性考察

目的制备氯雷他定口崩片并评价其稳定性.方法采用粉末直接压片法制备氯雷他定口崩片.以崩解时限和口感为评价指标,在预试验基础上,采用正交试验优化处方组成和制备工艺.按2005年版药典的规定评价其质量,通过影响因素试验,初步稳定性考察试验评价其稳定性.结果采用优化处方和工艺制备的氯雷他定口崩片口感良好,崩解时限为30s,10min溶出达95%,各项指标符合药典规定要求,稳定性良好.结论氯雷他定口崩片处方合理,制备工艺简单,适合工业生产.     

醋酸艾司利卡西平片的制备及其稳定性研究

目的:制备醋酸艾司利卡西平片并进行制剂稳定性研究。方法:以醋酸艾司利卡西平为主药,交联聚乙烯吡咯烷酮、预胶化淀粉等为辅料,采用等量递加法混合、直接压片制备片剂;按照2010年版《中国药典》要求对样品进行影响因素试验、加速试验和室温长期留样试验,以性状、溶出度、含量和有关物质含量等为指标考察制剂稳定性。结果:所制制剂在各项稳定性试验中考察指标均变化不大。结论:所制醋酸艾司利卡西平片对光、热、湿稳定,稳定性好,符合《中国药典》2010年版要求。     

Adaptive Design Space as an Integrated Component of Quality by Design

Introduction

The US Food and Drug Administration requires pharmaceutical companies to develop extensive process understanding prior to routine manufacturing of drug products. Through development and validation, drug manufacturers enhance their process understanding and identify an acceptable range of process parameters for each unit operation; this is referred to as the design space. Typically, limited work is done to study the effect of long-term raw material variations on the robustness of the design space. In the present study, the development of a design space for a tablet formulation containing two APIs (acetaminophen, caffeine) through a direct compression process was investigated.

Material and Methods

A design of experiment including different excipient ratios of microcrystalline cellulose and lactose, two croscarmellose sodium levels, four tablet compression forces, and four blend parameters was created using an industrial-size press to define a knowledge space. Quality attributes (disintegration time, dissolution, radial tensile strength, and friability) were measured and a design space derived. In order to test the robustness of the design space, raw material properties, specifically particle size of acetaminophen and ratio of lactose anhydrous to monohydrate, were modified. Also, compression parameters were varied.

Results

Tablets were analyzed for relevant critical quality attributes (CQAs) to investigate how variability in raw materials can change the design space. The modification of the process parameters was used as a means of compensating for raw material variability to produce tablets that met CQA requirements. An adaptive design space approach based on the adaptation of critical process parameters is proposed to facilitate the creation of tablets meeting specifications despite variation in raw material properties.     

乳糖粉体学性质的初步探讨

测定 5种型号乳糖产品的粒度分布、松密度、摇实密度、休止角、流速及成形性 ,确定何种乳糖适合用作直接压片辅料。以双氯芬酸钾为模型药物 ,用各型号乳糖为填充剂直接压片 ,制得双氯芬酸钾片 ,测定所得片子的硬度、脆碎度和片重差异。结果显示 :粒度以GranuLac 2 0 0最细 ,其他几种差不多 ;流动性以GranuLac 2 0 0最差 ,GranuLac 70次之 ,其他三种相差不大 ,成形性以Cellactosc 80最好 ,Tablettose70次之 ,CapsuLac 80最差。综合各项粉体学性质 ,Cellactose80和Tablettose 70较适合用作直接压片的辅料。用以上各型号乳糖作填充剂直接压片制得双氯芬酸钾片 ,其压片结果与上述测定结果基本相符 ,显示粉体学指标的测定对辅料的选择确有一定的指导作用     

Design and Development of Polyethylene Oxide Based Matrix Tablets for Verapamil Hydrochloride

In the present investigation an attempt has been made to increase therapeutic efficacy, reduced frequency of administration and improved patient compliance by developing controlled release matrix tablets of verapamil hydrochloride. Verapamil hydrochloride was formulated as oral controlled release matrix tablets by using the polyethylene oxides (Polyox WSR 303). The aim of this study was to investigate the influence of polymer level and type of fillers namely lactose (soluble filler), swellable filler (starch 1500), microcrystalline cellulose and dibasic calcium phosphate (insoluble fillers) on the release rate and mechanism of release for verapamil hydrochloride from matrix tablets prepared by direct compression process. Higher polymeric content in the matrix decreased the release rate of drug. On the other hand, replacement of lactose with anhydrous dibasic calcium phosphate and microcrystalline cellulose has significantly retarded the release rate of verapamil hydrochloride. Biopharmaceutical evaluation of satisfactory formulations were also carried out on New Zealand rabbits and parameters such as maximum plasma concentration, time to reach peak plasma concentration, area under the plasma concentration time curve_(0-t) and area under first moment curve_(0-t) were determined. In vivo pharmacokinetic study proves that the verapamil hydrochloride from matrix tablets showed prolonged release and were be able to sustain the therapeutic effect up to 24 h.     

A preliminary study of the effect of slug hardness on dissolution from hard gelatin capsules filled on an automatic capsule-filling machine

The effect of magnesium stearate on slug hardness and the dissolution of hydrochlorothiazide from hard gelatin capsules filled on an instrumented Zanasi automatic capsule-filling machine at constant compression force is reported. The fillers were microcrystalline cellulose and anhydrous lactose. Slug hardness was assessed by measuring the breaking load of slugs in a three-point bending test. With microcrysallire cellulose, t_60% first decreases to a minimum and then increases with increased lubricant levds, confirming the findings of Stewart et al. (1979). This is accompanied by a dramatic decrease in slug hardness. With lactose, t_60% increases with the lubricant level white slug hardness decreases slightly, although not significantly (5% level) at the levels tested. With microaystalline cellulose, it is proposed that the increased hydrophobtcity of the slug with increasing lubricant levels initially is more than offset by reduced slug hardness which probably enhances deaggregation and wetting of capsule contents.