体外释放度试验对茶碱缓释,控制制剂的评价

本文对四个厂家的茶碱缓释，控释制剂，在不同ｐＨ条件下作释放度试验，结果表明，各厂家生产的制剂在不同ｐＨ介质中释放速率不同，根据释放度试验获得的数据，按释放速率－介质ｐＨ时间，建立三维释放特性图，可作为药品质量控制手段，评价制剂方法，有利于制订药品标准。     

盐酸曲马多缓释片和胶囊剂的体外释放度对比研究

对盐酸曲马多缓释片和胶囊剂的体外释放模式及在不同ｐＨ条件下的体外累积释放度和释放速率进行对比研究。缓释片剂体外释放符合一级动力学模式,而缓释胶囊剂体外释放则符合Ｈｉｇｕｃｈｉ方程,二者在不同ｐＨ介质中的累积释放百分率及释放速率均有显著性差异（Ｐ〈０．０５）。表明两种盐酸曲马多缓释制剂体外释放模式存在差异。而且ｐＨ对二者的体外释放过程具有明显影响。     

不同厂家盐酸坦索罗辛缓释胶囊释放曲线对比研究

目的 ：通过对比不同厂家生产的已通过或视同通过一致性评价的盐酸坦索罗辛缓释胶囊样品在4种释放介质中的释放曲线，比较其体外释放差异。方法 ：分别以pH 6.8磷酸盐缓冲溶液、pH 4.0磷酸盐缓冲溶液、pH 1.2盐酸溶液和水作为释放介质测定释放曲线，其相似度用相似因子(f₂)法分析。结果 ：自研生产的3批产品在4种介质中的释放曲线均与参比制剂高度相似。A企业产品在4种介质中、C企业产品在3种介质中、B和D企业产品仅在2种介质的释放曲线与参比制剂相似。结论 ：不同厂家制剂的释放行为有很大差异。     

某国产卡马西平缓释片与参比制剂的释放度比较

比较了国内某一厂家3批卡马西平缓释片(受试制剂)与Tegretol(参比制剂)在不同pH介质中的体外释放度。采用桨板法,转速75 r/min,分别考察了受试制剂和参比制剂在不同释放介质(水、pH 4.5乙酸盐缓冲液和pH 6.8磷酸盐缓冲液)900 ml中的释放行为。结果显示,在上述3种介质中,受试制剂的批间差异显著,同批产品在不同介质中的释放行为也有显著差异。受试制剂的内在品质不如参比制剂。     

不同厂家盐酸二甲双胍缓释片体外释放度考察

目的对不同厂家的盐酸二甲双胍缓释片进行体外释放度考察,为临床合理用药提供依据。方法根据盐酸二甲双胍缓释片标准(进口药品注册标准JX20010451)及相关参考文献,采用溶出度转篮法的装置进行体外释放实验,以pH 6.8磷酸盐缓冲液1 000 mL为释放介质,转速为100 r·min-1,温度为(37±0.5)℃,用紫外分光光度法进行含量测定。分别对不同厂家的盐酸二甲双胍缓释片,进行体外释放试验,计算累积释放百分率,绘制释放曲线;计算f2相似因子。结果两种进口制剂的相似因子f2为93.54。不同国产制剂与进口制剂的相似因子f2依次为:47.80、48.10、49.67、66.27、47.65、70.53、67.05;各国产制剂与BIOVAIL制剂的相似因子f2依次为:49.21、49.49、51.25、67.00、49.05、68.22、67.21。结论不同国产制剂与进口制剂的体外释药行为存在明显差异。     

茶碱缓释片体内外试验的相关性

目的：评价茶碱缓释片的体外释放与体内吸收的相关性,为其质量控制提供实验依据。方法：用反相高效液相色谱法测定血浆中的茶碱浓度,按Ｗａｇｎｅｒ－Ｎｅｌｓｏｎ公式计算一定时间内２种茶碱缓释片的体内吸收百分率。在３种不同ｐＨ的介质中进行体外释放度试验,。计算相应时间内的累积释放百分率。结果：介质的ｐＨ变化对茶碱缓释片的体外释放度无明显影响。结论;茶碱缓释片的体内吸收百分率与体外释放百分率间存在良好的相关关     

硝苯地平缓释片及控释片的体外释放度试验

目的 对不同厂家硝苯地平缓、控释片的释放度进行考察，为评定药品的质量提供依据。方法 以pH=3．075的磷酸盐缓冲液为溶出介质，用紫外分光光度法对4个厂家的硝苯地平缓、控释片进行体外释放度测定和比较。结果A、B、C片体外释放符合一级动力学，D片符合零级动力学。结论 均能达到缓、控释目的，减少用药次数。     

双氯芬酸钠缓释制剂的释放度比较

目的：考察不同药厂双氯芬酸钠制剂的释放度，评价其内在质量。方法：按《中国药典》2000版释放度测定法，以磷酸缓冲液为释放介质，采用转篮法，用反相高效液相色谱法测定释放涟含量，进而计算其累积释放百分率并提取释放参数。结果：普通肠溶片释放最快，24．5min即释放85％以上，双释放控释片及双释放胶囊12h累积释放百分率均为80％以上。结论：三个厂家的双氯芬酸钠制剂均符合《中国药典》2000版规定。     

不同厂家非那雄胺片在4种溶出介质中的 溶出曲线比较研究

目的：比较不同厂家非那雄胺片在4种不同溶出介质中的溶出曲线,为全面评价药品质量提供依据。方法：采用桨法,以4种不同溶出介质各900 mL,转速为50 r?min-1,采用HPLC法,测定不同厂家非那雄胺片溶出曲线。结果：不同厂家的非那雄胺片在4种溶出介质中的溶出曲线不完全相似。结论：相关厂家应改进制剂的处方工艺,以改善制剂的溶出行为,提高药品质量。     

硝苯地平缓释片释放度研究

目的建立硝苯地平缓释片的释放度试验方法，对5个厂家生产的硝苯地平缓释片的含量和释放度进行测定。方法以0．5％吐温-80水溶液（900mL）作为溶出介质，采用桨法测定溶出度，转速为100r／min，温度为（37．0±0．5）℃；用反相高效液相色谱法测定含量，测定波长为333nm。结果用建立的方法可以准确地测定各厂家硝苯地平缓释片的释放度，不同厂家生产的硝苯地平缓释片释放速度差别较大。结论对不同厂家生产的硝苯地平缓释片释放度进行检查，有助于控制产品质量。     

Riociguat for the treatment of pulmonary hypertension: a safety evaluation

ABSTRACT

Introduction: The development of pulmonary hypertension (PH) has multifactorial underlying pathophysiological causes and can be classified into five groups. While three different classes of therapeutic drugs are licensed for the treatment of pulmonary arterial hypertension (PAH, WHO group 1), specific medical therapies are lacking for other forms of PH, such as PH due to left heart disease. In 2013 riociguat, a first-in class soluble guanylate cyclase stimulator, has also become available for the treatment of PAH. Riociguat was further introduced as the first approved pharmacotherapy for the treatment of patients with chronic thromboembolic PH (WHO group 4, CTEPH). Despite these advances in therapeutic options for patients with PH, none of these agents have been approved for the treatment of PH due to left heart disease.

Areas covered: We aim to give an overview of the pathophysiology of PH, pharmacodynamics and pharmacokinetic properties, safety and efficacy of riociguat, including adverse events, contraindications and drug interactions.

Expert opinion: Considering the increasingly broad indications for riociguat in patients with PH, substantial knowledge of data and properties on safety and efficacy of riociguat are becoming more and more important for physicians prescribing riociguat to PH patients.     

Exploration of Novel Co-processed Multifunctional Diluent for the Development of Tablet Dosage Form

The aim of this investigation was to develop a novel multifunctional co-processed diluent consisting of microcrystalline cellulose (Avicel PH 102), crospovidone (Polyplasdone XL) and polyethylene glycol 4000. Colloidal silicon dioxide and talc were also incorporated as minor components in the diluent to improve tableting properties. Melt granulation was adopted for preparation of co-processed diluent. Percentage of Avicel PH 102, Polyplasdone XL and polyethylene glycol 4000 were selected as independent variables and disintegration time was chosen as a dependent variable in simplex lattice design. The co-processed diluent was characterised for angle of repose, bulk density, tapped density, Carr''s index, percentage of fines and dilution potential study. Acetaminophen and metformin were used as poorly compressible model drugs for preparation of tablets. The blend of granules of drug and extra-granular co-processed diluent exhibited better flow as compared to the blend of drug granules and physical mixture of diluents blend. The diluent exhibited satisfactory tableting properties. The tablets exhibited fairly rapid drug release. In conclusion, melt granulation is proposed as a method of preparing co-processed diluent. The concept can be used to bypass patents on excipient manufacturing.     

Tableting properties of microcrystalline cellulose obtained from wheat straw measured with a single punch bench top tablet press

The objective of this work was to study the relation between the manufacturing conditions of microcrystalline cellulose (MCC), its physicochemical properties and its tableting behavior. Two different preparation procedures were used to produce MCC from wheat straw, utilizing an acid hydrolysis method, either using only sulfuric acid or combination of sulfuric and hydrochloric acid. The tableting behavior of obtained MCC samples and mixtures of MCC with ibuprofen was studied using a dynamic powder compaction analyzer. It was observed that some of the obtained MCC samples showed better flowing properties than commercially available Vivapur® PH101 and also very high values of tensile strength, solid fraction and elastic recovery. This can be linked with its good compaction behavior, but on the other hand it can cause problems with the disintegration of the tablets. In mixtures with ibuprofen, MCC samples showed lower values of tensile strength, while on the other hand elastic recovery did not seem to be much affected, still exhibiting very high values. According to the obtained results, it can be concluded that MCC obtained from the agricultural waste could have satisfactory properties for tablet preparation by the direct compression method. Further studies are needed to optimize process conditions in order to achieve better physicochemical characteristics, especially in terms of elastic recovery.     

Influence of formulation and excipient variables on the pellet properties prepared by extrusion spheronization

Four commercial grades of microcrystalline cellulose, Avicel PH 101, Avicel PH 102, Avicel PH 112 and Avicel PH 302 were compared for extrusion spheronization. Model mixes containing Avicel PH 101 with different proportions of fillers like lactose and dicalcium phosphate dihydrate (DCPD) were also compared to observe the influence of these fillers on the pellet properties. The amount of water used for granulation of Avicel/ Avicel mixes was kept constant so as to evaluate and quantitate the influence of these excipients/fillers on the pellet properties. The various pellet properties evaluated included, drug release, size and size distribution, shape, density, friability and flow. Mean pellet diameter did not vary among the Avicel grades. Pellets prepared with different proportions of Avicel PH 101 and lactose were more or less similar in mean diameter. The same phenomena were observed in case of DCPD as well. Plain lactose pellets were the largest in size. Therefore, it can be inferred that the presence of Avicel suppressed the change in pellet size. Circularity was found to be significantly linear function of log of bulk density of Avicel powders. As revealed by the SEM photographs, pellets of Avicel PH 101 were fairly round where as those containing Avicel PH 302 were dumbbell shaped. Formulations containing DCPD showed the highest circularity. Drug release rate varied in all the formulations. Among the Avicel grades, Avicel PH 302 showed the highest drug release rate where as Avicel PH 101 showed the least. Drug release also varied as a function of the type of filler and their proportion in the pellets. For both the fillers, the drug release increased with an increase in their proportion. Less water was required for formulations containing higher amounts of lactose and DCPD. Plain DCPD failed to spheronize, although pellets of plain lactose could be formed at the investigated level of water.     

转化生长因子β1血清水平与左向右分流型先天性心脏病肺动脉压力的相关性探讨

目的 通过对先天性心脏病及先天性心脏病伴肺动脉高压（PH）患者血清中转化生长因子β1（TGF-β1）水平的检测,进一步明确其与先天性心脏病伴肺动脉高压的关系.方法 采用实验研究策略,利用酶联免疫吸附测定（ELISA）方法测定48例先天性心脏病患儿（4组分为无PH组、轻度PH组、中度PH组、重度PH组各12例）静脉血清中TGF-β1的水平变化.结果 TGF-β1在重度PH组（2.01±0.26）μg/L明显高于中度PH组（1.80±0.56）μg/L、轻度PH组（1.34±0.11）μg/L及无PH组（0.82e±0.11）ug/L（P＜0.01）,尤以重度与无PH之间较为明显,差异具有统计学意义（P＜0.01）.结论 左向右分流型先天性心脏病患儿TFG-β1参与先天性心脏病伴肺动脉高压的形成,可能对先天性心脏病伴肺动脉高压程度的评价、手术指征及预后起着重要作用.     

不同厂家盐酸克林霉素胶囊溶出度的比较

目的：考察在不同PH值溶出介质中.不同厂家盐酸克林霉素胶囊的体外溶出情况.方法：采用桨法,转速50转/分钟.不同PH值的溶出介质900ml.测定溶出度,绘制溶出曲线.结果：显示在PH1.2.PH4.0.PH6.8.水的溶出介质中.各厂家的胶囊溶出曲线有较大差异.结论：盐酸克林霉素胶囊的内在质量需进一步提高.     

Riociguat for the treatment of pulmonary hypertension

INTRODUCTION: Pulmonary hypertension (PH) is a severe condition with a poor prognosis despite recent treatment advances. Therapies with new mechanisms of action are needed. AREAS COVERED: This review will help readers understand the mechanism of action of the soluble guanylate cyclase (sGC) stimulator riociguat (BAY 63-2521) and will provide a comprehensive summary regarding efficacy and safety of this drug in the management of PH. The most relevant publications up to December 2010 were used as sources for this review. EXPERT OPINION: Cyclic guanosine monophosphate (cGMP) is an important mediator of the preferential perfusion of well-ventilated regions throughout the lung. Drugs that increase cGMP levels could promote pulmonary vasorelaxation while maintaining optimal gas exchange. cGMP is generated by sGC, which can be stimulated by nitric oxide (NO). Riociguat stimulates sGC independently of NO and increases the sensitivity of sGC to NO, resulting in increased cGMP levels. Results to date suggest rapid, potent and prolonged efficacy and good tolerability in different types of PH. Phase III clinical trials are evaluating the long-term safety and clinical effectiveness of riociguat in pulmonary arterial hypertension (PAH) and chronic thromboembolic PH. Riociguat has the potential to become an important drug for the treatment of patients with PH.     

Determination of iodine values using 1,3-dibromo-5,5-dimethylhydantoin (DBH) without the employment of chlorinated hydrocarbons. Analytical methods of pharmacopoeias with DBH in respect to environmental and economical concern. Part 17

Low and medium iodine values of fixed oils and fats can be determined in glacial acetic acid within reduced waiting times of only 5 min. Highly unsaturated compounds such as those of linseed oil, cod-liver oil, sunflower oil, soybean oil, wheat germ oil and the emulsifier sorbitan trioleate result too low values in comparison to PH. EUR. 2002 [2] and USP 2000 [3]. Cocoa butter with a low iodine number is insoluble in glacial acetic acid. The iodine values of nonionogenic emulsifiers such as ceteareth-30 (Macrogol cetostearyl ether PH. EUR. 2002), oleth-10 resp. 20 (Macrogol oleyl ether PH. EUR. 2002) and polysorbate-80 PH. EUR. 2002 are obtained in aqueous solutions. Oleth-2 (Macrogol oleyl ether PH. EUR. 2002), polyoxyl-40 castor oil (Macrolglycerol ricinoleate PH. EUR. 2002), polysorbate-60 PH. EUR. 2002 and sorbitan trioleate PH. EUR. 2002 need the addition of ethyl acetate. Fixed oils even with high iodine values can be determined in an o/w emulsion with a reaction time of 5 min in most cases, when nonionogenic emulsifiers such as ceteareth-30, polyoxyl-30 glycerol monolaurate or polyoxyl-60 hydrogenated castor oil (Macrolglycerol hydroxystearate PH. EUR. 2002) are used.     

萘普生钠伪麻黄碱缓释片的处方工艺研究及体外释放度考察

目的研究萘普生钠伪麻黄碱缓释片的制备方法,筛选出最佳处方制备工艺条件。方法采用正交设计,以HPMC K15M、微晶纤维素(PH101)和乳糖的用量及缓释片的硬度为因素进行试验,确定出最佳制备工艺条件;并对优化的试验结果进行验证,同时考察其体外释放效果。结果缓释层最佳工艺条件:HPMC K15M、PH101、乳糖的用量分别为150mg、40mg、60mg,压片硬度8kg;所制备的样品在1、2、4h的体外累积释放率分别为43.62±1.81%、68.81±1.52%、95.22±1.07%。结论制备的萘普生钠伪麻黄碱缓释片的缓释效果与设计值基本吻合,工艺重现性好,体外累积释放率符合要求。关键词:萘普生钠盐酸伪麻黄碱双层缓释片正交试验设计制备工艺体外累积释放率     

IL-6在肺动脉高压中的研究进展

白细胞介素-6 (interleukin-6,IL-6)是一种多效性细胞因子,在炎症反应中起重要作用。越来越多的证据表明,IL-6在肺动脉高压(pulmonary hypertension,PH)的发生发展中也起到了十分重要的作用,具体体现在：PH患者和动物模型的循环中IL-6水平明显升高,小鼠体内过表达IL-6可以诱导重度PH,针对IL-6的治疗可以改善PH。本文主要从分子水平对IL-6在PH中的作用及其机制的研究进展进行综述,并对目前以IL-6为靶点治疗PH的候选方案进行介绍,以期为PH的临床药物研究开发提供参考。