奥美拉唑在不同pH介质中的释放曲线及其在肠溶制剂质量评价中的应用

目的 探讨已上市肠溶制剂的质量评价方法.方法按照日本“药品品质再评价工程”的相关方法,测定奥美拉唑肠溶制剂在pH1.0、pH6.0、pH6.8缓冲液及纯化水中的释放曲线.结果奥美拉唑肠溶制剂在不同pH介质中的释放行为存在极显著性差异.结论采用不同pH介质中释放曲线的测定结果来评价肠溶制剂更能区分其内在质量.     

熔融挤出法制备阿司匹林肠溶颗粒

目的优化熔融挤出法制备阿司匹林肠溶颗粒的配方和方法。方法以pH值1.2介质中耐酸性与pH值6.8介质中的溶出度为评价指标;以星点设计方法优选肠溶材料与辅料配比。结果以79.8%醋酸羟丙甲纤维素琥珀酸酯为肠溶材料,4.2%十八醇为释药调节剂,3.0%微粉硅胶为润滑剂,于130℃下挤出,过程顺利,颗粒均一;所得载药颗粒在pH值1.2盐酸中2 h溶出(9.1±0.56)%,在pH值6.8缓冲液中45 min溶出(72.42±3.06)%。结论熔融挤出法制备阿司匹林肠溶颗粒简便、可靠。     

多潘立酮片体外溶出的一致性评价

目的 考察原研地产化参比制剂的质量,比较参比制剂与国产仿制制剂的溶出一致性并制备与参比制剂溶出相似的自制制剂.方法 建立了多潘立酮UV的体外溶出测定方法,以pH1.2、pH6.0、pH6.8和水为溶出介质考察三个批次的参比制剂、三种国内市售仿制制剂以及自制制剂的溶出行为,采用溶出相似因子(f2)法评价溶出行为的相似性....     

双嘧达莫肠溶固体分散物的形成及其体外溶出度的研究

目的采用固体分散技术改善pH依赖型难溶药物双嘧达莫的体外溶出行为.方法以L-型肠溶丙烯酸树脂(Eudragit L)为载体,将药物与Eudragit L的混和有机液喷包于微晶纤维素(MCC)空白丸芯上形成膜衣骨架型共沉淀物结构,利用X射线衍射,扫描电镜等方法研究固体分散物中双嘧达莫的晶体性质,考察不同比例组成的固体分散物的累积溶出百分率.结果肠溶固体分散物中药物的晶型消失,随载体比例增大,药物在人工胃液中的溶出减缓,在人工肠液中的释放加快.结论药物经固体分散技术处理后以无定型态分散于载体中,溶出行为显著改善.     

地红霉素肠溶微丸的制备及处方优化

目的制备地红霉素肠溶微丸.方法采用离心造粒法制备地红霉素微丸,流化床进行肠溶包衣.结果制备的地红霉素肠溶微丸在pH 1.2盐酸溶液中2 h的释放度＜10%,在pH 6.8磷酸盐缓冲液中45 min的释放度＞80%.结论本方法制备地红霉素肠溶微丸工艺可行,质量可靠.     

制剂质量特性测量的方法学研究

关于制剂质量特性的测量,一般涉及检测仪器与方法的设计,或对已有方法的改进或讨论,大都属于探索性工作,可供动向参考。无线电遥测法评价肠溶衣性能 Dressman等为考察肠溶衣性能,设计了本实验。其构思为:将适量枸椽酸-枸椽酸盐配制或pH3、4及5的缓冲物,加辅料制片,以羟丙基甲基纤维素邻苯二甲酸酯包作肠溶衣。由于胃液的pH一般为1～3;小肠液pH为5～7。如该片剂在胃中破裂时,引起pH值上升,如在小肠部崩溶,则引起肠液pH下     

生产工艺参数对奥美拉唑肠溶片释放度的影响

目的研究影响奥美拉唑肠溶片质量的生产工艺参数。方法用同一种包衣预混剂试验,分别考察肠溶衣层增重、包衣混悬液pH、包衣温度3个因素对奥美拉唑肠溶衣片释放度的影响。结果肠溶衣层增重越大,耐酸力越强,但同时会使释放度越小;包衣混悬液pH在一定范围内对释放度无影响;包衣温度过低出现粘片,包衣温度越高,耐酸力越弱,但同时会使释放度越大。结论当肠溶衣增重10.0%时,肠溶效果最理想;包衣液pH在6.0～7.2时,对肠溶效果影响小;包衣温度在36～39℃时,奥美拉唑肠溶片包衣操作较顺利,且释放度较好。     

硝苯地平缓释片溶出曲线对比研究

目的:对自研硝苯地平缓释片与参比制剂进行体外溶出曲线对比研究,为质量一致性评价提供依据.方法:考察硝苯地平缓释片(Ⅱ)与参比制剂在pH 1.2盐酸盐缓冲液、pH 4.0醋酸盐缓冲液、pH 6.8磷酸盐缓冲液和水4种溶出介质中的体外溶出行为和一致性,并采用乙醇诱导剂量倾泻和高转速试验进一步考察两者的相似性.结果:自研硝苯...     

不同厂家复方黄连素片的溶出曲线研究

目的比较不同企业的复方黄连素片在4种溶出介质中的溶出曲线,为该制剂的质量评价提供参考。方法分别在水、0.1 mol.L-1盐酸、pH 5.9和pH 7.4磷酸盐缓冲液中,测定15个厂家复方黄连素片的溶出曲线,并用f2因子法分析结果。结果在水中有4个厂家的样品与参比制剂溶出过程一致,在0.1 mol.L-1盐酸中有3个厂家与参比制剂一致,在pH 5.9和pH 7.4缓冲液中分别仅有1个厂家与参比制剂一致。结论多数厂家与参比制剂的溶出曲线有显著差异,建议对溶出度进行规定以提高该药品质量。     

对某国产盐酸二甲双胍肠溶胶囊溶出度的评价研究

目的：评价盐酸二甲双胍肠溶胶囊在不同p H条件下的溶出曲线。方法：参照2010版《中华人民共和国药典》附录X B、XD,采用桨法考察盐酸二甲双胍肠溶胶囊在pH分别为1.0、4.0、纯水条件下2h后调节为pH6.8磷酸缓冲液再溶出1h的溶出性能, HPLC法测定溶出液中二甲双胍浓度,DDSolver 1.0对溶出曲线进行分析。结果：盐酸二甲双胍肠溶胶囊在pH1.0、pH4.0及纯水2h内几乎不释放,而在pH6.8的磷酸盐缓冲液中45min内释放达90%以上。经软件DDSolver1.0分析3种pH条件下的溶出曲线是相似的。结论：该二甲双胍肠溶胶囊在不同pH条件下的溶出曲线是相似的,对于不同患者溶出性能一致,药品品质较佳。     

Formulation and evaluation of primaquine phosphate taste-masked rapidly disintegrating tablet

This work investigates the complete bitter-taste-masking of primaquine phosphate (PRM) using a solid dispersion with mono ammonium glycyrrhyzinate pentahydrate (GLY). This work also describes the preparation of rapidly disintegrating tablets (RDTs) of PRM by a direct compression method using superdisintegrant, croscarmellose sodium. A solid dispersion was prepared by the solvent evaporation method. Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) were performed to identify the physicochemical interaction between drug and carrier, hence its effect on dissolution. In-vitro drug release studies were performed for RDTs at both pH 1.2 and 6.8. Bitterness score was evaluated using a human gustatory sensation test. FTIR spectroscopy and DSC showed no interaction of PRM in GLY solid dispersion. RDTs prepared from solid dispersion showed complete bitter-taste-masking of PRM. RDTs containing solid dispersion exhibited a better dissolution profile, at both pH 1.2 and 6.8, than pure PRM. Thus, the solid dispersion technique can be successfully used for complete bitter taste masking of PRM.     

乳化溶剂扩散法制备罗红霉素肠溶微球及影响因素考察

目的罗红霉素肠溶微球的制备及影响因素考察。方法应用肠溶高分子材料 ,采用乳化溶剂扩散法一步制备罗红霉素肠溶微球。对影响微球形态、粒度分布、收率及其在 0 . 1mol·L-1盐酸溶液和 pH 6 8磷酸盐缓冲溶液中累积释放度的处方因素、制备条件和溶剂系统进行了考察。应用X 射线粉末衍射实验考察了药物在微球中的分散状态。结果制备的微球外观圆整。微球粒径随着搅拌转速的增加而减小。微球收率随架桥剂用量减少 ,良溶剂用量增加而增加 ;并且受到不良溶剂中乳化剂种类的影响。药物在 0 . 1mol·L-1盐酸溶液中的释放速率随肠溶材料HP- 5 5用量增加显著降低。当HP- 5 5与药物质量比大于 5时 ,药物在 0 . 1mol·L-1盐酸溶液中释放小于 5 % (w) ,同时在pH 6 . 8磷酸盐缓冲溶液中可迅速释放。X- 射线粉末衍射结果显示 ,微球中药物已被高度分散 ,形成固体分散体。结论乳化溶剂扩散法适用于制备具有固体分散体结构的肠溶微球。     

吲哚美辛肠溶滴丸的研制及其体外释药研究

研制吲哚关辛（IDM）肠溶滴丸,并考察其体外释药特性。方法：选用PEG6000为基质,用正交试验筛选IDM滴丸的最佳处方及工艺,并采用聚丙烯酸树脂Ⅱ为肠溶材料对其进行包衣,制备IDM肠溶滴丸。转篮法对其体外释药特性进行考察,并与市售IDM肠溶片进行比较。结果：筛选出IDM滴丸最佳制备条件为：IDM与总基质的质量比为1：3,滴速为65滴／min,滴制温度为90℃,冷凝液温度为5℃。IDM肠溶滴丸及市售IDM肠溶片在酸性介质中几乎不释药,而在pH为6.8的磷酸盐缓冲液中,IDM肠溶滴丸的释药速度显著高于市售肠溶片（P〈0．05）。结论：IDM肠溶滴丸具有明显肠溶效果,同时可加快IDM在肠道中的释放速度,值得进一步研究。     

无时滞非达霉素肠溶片的制备及溶出评价

目的: 制备无时滞非达霉素肠溶片,考察其溶出特性。方法: 采用湿法制粒工艺,通过正交实验进行片芯优化,以甲基丙烯酸与丙烯酸乙酯共聚物为肠溶包衣材料,制备非达霉素肠溶片,以体外释放度为指标,考察其溶出行为。结果: 片芯中羟丙甲纤维素和交联羧甲基纤维素钠的用量分别为1.2%和4.5%,微晶纤维素和淀粉的比例为3:1,肠溶层共聚物的比例为50%时,制备的非达霉素肠溶片在pH1.0盐酸中2h释放度小于10%,在pH4.5醋酸盐缓冲液中可以崩解释放,在pH6.8磷酸盐缓冲液中快速释放,10min释放度大于60%。结论: 制备的非达霉素肠溶片与普通肠溶片相比无时滞效应,有望进行工业化生产。     

Design of a drug delivery system with bimodal pH dependent release of a poorly soluble drug

A delivery system which provides bimodal pH dependent release of poorly water soluble carvedilol in gastric and intestinal environment was designed. Preparation of solid dispersion with porous silica ensured a significantly higher dissolution rate of carvedilol in acidic and alkaline media in comparison to pure drug, while granulation of that solid dispersion with enteric polymer dispersion resulted in diminished immediate release in acidic media and fast release of the remaining drug in alkaline media. The ratio in quantities of first vs. second release was controlled with amount of enteric polymer dispersion used for granulation process. Desired 25 mg release of carvedilol at pH values 1.2 and 6.8 was achieved when 1.80 g of polymer per 1.0 g of solid dispersion (drug to silica ratio= 0.25 g : 2.0 g) was used.     

尼群地平固体分散体及其片剂的体外溶出度评价

目的:运用固体分散技术提高尼群地平的体外溶出速率.方法:采用紫外分光光度法测定药物浓度,以体外溶出为指标,对固体分散体的载体、制备方法及比例进行优化.通过粉末直接压片法制备尼群地平固体分散片,根据日本橙皮书的要求对片剂的体外溶出进行考察.结果:采用泊洛沙姆188为载体,药物与载体比例为1:5,通过熔融法制备的固体分散体体外溶出效果较好,且制成的片剂,在4种介质(含0.15％吐温-80的水溶液、pH 1.2盐酸溶液、pH 4.0醋酸盐缓冲液、pH 6.8磷酸盐缓冲液)中,45 min时最低累积溶出度达80.3%.结论:通过固体分散技术制备的尼群地平片体外溶出能满足日本橙皮书的要求,且工艺简单、易于实施.     

硝苯地平缓释凝胶的制备工艺及其释药性能研究

目的:制备硝苯地平缓释凝胶并考察其体外释药情况。方法:采用复凝聚法制备硝苯地平缓释凝胶,以壳聚糖、海藻酸钠的浓度、搅拌速度和壳聚糖溶液与海藻酸钠溶液的体积比为因素进行正交试验;用转篮法测定所制凝胶的释放度,通过改变释放介质的pH值,考察该缓释药物对pH的敏感性。结果:最佳工艺为壳聚糖浓度0.4%、海藻酸钠浓度1.5%、搅拌速度160r.min-1、壳聚糖溶液与海藻酸钠溶液的体积比为6:1。硝苯地平缓释凝胶在pH1.5的人工胃液中4h释放度为13.43%;在pH6.8的人工肠液中4h释放度为52.30%,12h释放度为81.72%。结论:所制硝苯地平缓释凝胶具有明显的缓释作用,体外释放具有较强的pH敏感性。     

Design and evaluation of fast dissolving tablets of clonazepam

In the present work, fast dissolving tablets of clonazepam were prepared by direct compression method with a view to enhance patient compliance. Three super-disintegrants, viz., crospovidone, croscarmellose sodium and sodium starch glycolate in different ratios with microcrystalline cellulose (Avicel PH-102) along with directly compressible mannitol (Pearlitol SD 200) to enhance mouth feel. The prepared batches of tablets were evaluated for hardness, friability, drug content uniformity, wetting time, water absorption ratio and in vitro dispersion time. Based on in vitro dispersion time (approximately 13 s), three formulations were tested for the in vitro drug release pattern (in pH 6.8 phosphate buffer), short-term stability (at 40°/75% relative humidity for 6 mo) and drug-excipient interaction (IR spectroscopy). Among the three promising formulations, the formulation prepared by using 10% w/w of crospovidone and 35% w/w of microcrystalline cellulose emerged as the overall best formulation (t(50%) 1.8 min) based on the in vitro drug release characteristics compared to conventional commercial tablet formulation (t(50%) 16.4 min). Short-term stability studies on the formulations indicated that there were no significant changes in drug content and in vitro dispersion time (P<0.05).     

氟比洛芬肠溶片的制备及其体外释放度研究

目的:制备氟比洛芬肠溶片并考察其体外释放特性。方法:以乙基纤维素(EC)、甲基丙烯酸共聚物(Eudragit S100)、乳糖为辅料,采用直接压片法制备制剂;考察处方中不同辅料用量对药物释放的影响及其在0.1mol·L-1盐酸溶液(HCl)和pH6.8磷酸盐缓冲液(PBS)中的体外释放特性。结果:以EC0.250g、Eudragit S1000.750g、乳糖3.750g时组成的处方可在HCl中不释放,在PBS中完全释放达94.20%。结论:该制剂处方设计和制备方法可行,其释放行为符合设计要求。     

Formulation design and optimization of fast dissolving clonazepam tablets by sublimation method

Fast dissolving tablets of clonazepam were prepared by sublimation method with a view to enhance patient compliance. A 3(2) full factorial design was applied to investigate the combined effect of two formulation variables: amount of croscarmellose sodium and camphor. Croscarmellose sodium (2-8% w/w) was used as superdisintegrant and camphor (20-40% w/w) was used as subliming agent, to increase the porosity of the tablets, since it helps water to penetrate into the tablets, along with directly compressible mannitol to enhance mouth feel. The tablets were evaluated for hardness, friability, thickness, drug content uniformity, in vitro dispersion time, wetting time and water absorption ratio. Based on in vitro dispersion time (approximately 11 s); the formulation containing 5% w/w croscarmellose sodium and 40% w/w camphor was found to be promising and tested for in vitro drug release pattern (in pH 6.8 phosphate buffer). Short-term stability (at 40°/75% relative humidity for 3 mo) and drug-excipient interaction. Surface response plots are presented to graphically represent the effect of independent variables on the in vitro dispersion time. The validity of the generated mathematical model was tested by preparing two extra-design checkpoints. The optimized tablet formulation was compared with conventional commercial tablet formulation for drug release profiles. This formulation showed nearly nine-fold faster drug release (t(50%) 1.8 min) compared to the conventional commercial tablet formulation (t(50%) 16.4 min). Short-term stability studies on the formulation indicated that there are no significant changes in drug content and in vitro dispersion time (P<0.05).