芫花宫颈栓的制备研究

本实验对芫花的提取工艺、剂型进行了研究,将芫花提取物制成宫颈栓,改变了给药途径,解决了经羊膜注射给药给患者带来的痛苦,局部用药血药浓度大,引产时间缩短,制备工艺简单,成本低,易于推广。     

双氯芬酸钠栓与对乙酰氨基酚栓治疗小儿急性发热对比分析

目的:探讨双氯芬酸钠栓剂和对乙酰氨基酚栓在儿科临床的退热效果和安全性,为临床选择退热药提供参考。方法:100例急性发热患儿随机分为观察组和对照组,观察组予双氯芬酸钠栓0.5 mg/(kg.次),肛门给药;对照组予对乙酰氨基酚栓10mg/(kg.次),肛门给药。结果:观察组的起效时间[(41.63±3.71)min]短于对照组[(55.19±5.11)min],维持正常体温的时间[(7.31±1.62)h]长于对照组[(6.57±1.73)h],两组比较差异均有统计学意义(P<0.01)。结论:双氯芬酸钠栓对高热患儿具有退热作用快,维持时间长,使用方便、安全,无明显胃肠道反应等特点。     

上感口服液抗炎解热作用的研究

目的:研究上感口服液抗炎解热等药效作用,方法:观察上感口服液对二甲苯所致小鼠耳廓炎性肿胀的影响,对静脉注射脱脂牛奶致家兔发热的影响。对静脉注射刚果红后小鼠吞噬细胞吞噬功能的影响。以及对金黄色葡萄球菌、溶血性链球菌、白色葡萄球菌的体外抑制作用。结果:该药可抑制动物耳廓炎症,有较好的解热作用,可增强吞噬细胞功能,可明显抑制α溶血性链球菌、白色葡萄球菌生长。结论:上感口服液可拮抗急性渗出性炎症,增加非特异性免疫功能,有较好的解热、抑菌作用。     

Enhanced Intestinal Absorption of Cyclosporine in Rats Through the Reduction of Emulsion Droplet Size

The intestinal absorption of cyclosporine was measured in situ in rats using an olive oil emulsion prepared by either stirring or homogenization. The surface area of the homogenized dosage form was twice that of the stirred dosage form. The apparent permeability of cyclosporine from the homogenized emulsion was about twice that of the emulsion prepared by stirring. The examination of absorption in different intestinal segment lengths suggested the presence of an absorption window. The absorption of cyclosporine appeared to be concentration independent and, therefore, non-carrier mediated. The dependence of absorption upon the intestinal perfusion rate suggested that the stagnant aqueous layer is the rate-limiting barrier in cyclosporine absorption. These results indicate that the bioavailability of cyclosporine administered in an emulsion can possibly be increased by enhancing its rate of absorption through the reduction of droplet size.     

固体口服制剂的相转化研究进展

固体口服制剂的相转化研究对选择工艺流程和研发新产品有重要意义。根据相转化机制，固相相变可以分为3种类型：多晶型的转化（polymorphic transition），水化与脱水（hydration／dehydration），玻璃化相与结晶（vierfication/crystallization）的相互转化。固体口服新制剂研究中应重视药物多晶型和无定形现象，预防和防治固相处方设计与工艺流程选择中发送的相转化。     

高效液相色谱法测定对乙酰氨基酚口服溶液的含量

目的 　建立高效液相色谱法测定对乙酰氨基酚口服溶液中对乙酰氨基酚的含量 ,方法 　 Alltech-C1 8柱为固定相 ,甲醇 -水 (2 0∶ 80 )为流动相 ,检测波长 :2 44 mm,用外标法定量。 结果 　线性范围 :对乙酰氨基酚在 12 μg· m L- 1～ 12 0 μg· m L- 1浓度范围呈良好线性关系。 A=-13 5 0 2 .760 8+ 783 0 4.5 789C,r=0 .999。测得 3批的回收率分别为 98.7%、98.5 %、97.8% ,RSD分别为 0 .5 9%、0 .64 %、0 .42 %。结论 　本法简便快捷、结果准确 ,适用于对乙酰氨基酚口服溶液的含量测定。     

口服固体制剂掩味技术的研究进展

综述各种新兴口服固体制剂掩味技术的原理、特点及制备过程,并简述口服掩味技术评价方法的最新进展。口服固体制剂中许多药物由于受到不良口味的影响,致使病人的用药顺应性差、临床应用受限。近年来在使用矫味剂、麻痹剂等掩味手段的基础上产生了许多新兴的掩味技术,如喷动床包衣、粉末包衣和盐析包衣等。     

Improved dissolution behavior of lipophilic drugs by solid dispersions: the production process as starting point for formulation considerations

Introduction: Many new drug substances have low aqueous solubility which can cause poor bioavailability after oral administration. The application of solid dispersions is a useful method to increase the dissolution rate of these drugs and thereby improve their bioavailability. So far, several methods have been developed to prepare solid dispersions. To obtain a product with the desired attributes, both the formulation and production processes should be considered.

Areas covered: The most currently used methods to produce solid dispersions, such as the fusion method, hot melt extrusion, spray drying, freeze drying and supercritical fluid precipitation, are reviewed in this paper. In addition, the physicochemical characteristics of the obtained solid dispersions are discussed.

Expert opinion: Solid dispersions can be successfully prepared by simple fusion, hot melt extrusion, spray drying, freeze drying and supercritical fluid precipitation. Hot melt extrusion, spray drying and freeze drying are processes that can be applied for large scale production. The simple fusion method is not very suitable for large scale production, but is particularly suitable for screening formulations. The most recent method to produce sold dispersions is supercritical fluid precipitation. The process conditions of this method need extensive investigation, in particular in relationship with the selection of the type of carrier and/or solvent. Both processes and formulation aspects strongly affect the characteristics of solid dispersion products. Furthermore, application of crystalline solid dispersions is gaining increasing interest because they are thermodynamically more stable than amorphous solid dispersions.     

含对乙酰氨基酚的感冒药及柴芩清宁胶囊对脂多糖和干酵母大鼠发热模型的解热作用研究

目的 研究含对乙酰氨基酚的西药对乙酰氨基酚片、复方氨酚烷胺片、美扑伪麻片及中成药柴芩清宁胶囊对脂多糖（LPS）及干酵母大鼠发热模型的解热作用。方法 制备大鼠100 μg/kg LPS及20%干酵母发热模型;乙酰氨基酚片、复方氨酚烷胺片、美扑伪麻片高、中、低剂量分别为205.67、102.83、51.42 mg/kg,以对乙酰氨基酚计;柴芩清宁胶囊高、中、低剂量分别为1110.60、555.30、277.65 mg/kg,以胶囊内容物质量表示,ig给药。观察大鼠体温变化,计算平均最大体温上升高度（△T）及体温反应指数（TRI）,绘制平均升温曲线。结果 对乙酰氨基酚片、复方氨酚烷胺片、美扑伪麻片及柴芩清宁胶囊各剂量组对LPS及干酵母大鼠发热模型均具有显著解热作用,且均存在一定剂量效应关系。结论 对乙酰氨基酚片、复方氨酚烷胺片、美扑伪麻片及柴芩清宁胶囊对LPS及干酵母大鼠发热模型均有一定解热作用,3种西药的解热作用起效快但是作用时间短,而柴芩清宁胶囊表现为起效慢但是作用时间长。     

Optimization of a Vaginal Suppository Formulation to Deliver SHetA2 as a Novel Treatment for Cervical Dysplasia

Cervical dysplasia induced by the human papilloma virus unpredictably progresses to cervical cancer. Therapeutic options are invasive and affect the patient's quality of life. SHetA2 has demonstrated therapeutic efficacy against human and murine human papilloma virus–induced tumors, but its oral bioavailability is <1%. An optimized vaginal suppository formulation can deliver SHetA2 in sufficient doses to prevent cervical dysplasia. The quality by design approach was employed to optimize the suppository formulation consisting of cocoa butter as base with 5% Kolliphor and 40% SHetA2. The suppository had a content uniformity of 105.44 ± 0.42%, melted in <8 min, and had a complete release of SHetA2 in water. Administration of the suppository to mice-achieved cervix concentrations that were significantly higher than the SHetA2 therapeutic concentration, with the maximum concentration (C_max-cervix = 336.78 μg/g) being more than 100-fold the therapeutic SHetA2 concentration. Furthermore, the levels of cyclin D1 protein decreased 9-fold indicating a correlation of drug concentrations with the pharmacodynamic endpoint. These proof-of-concept studies suggest that the SHetA2 optimized vaginal suppository formulation may have a potential use in the prevention of cervical dysplasia, but detailed efficacy studies are required to confirm this assumption.     

氮酮对扑热息痛渗透裸鼠皮肤的促透作用

以裸鼠皮肤为隔膜的上下扩散的２个简单扩散小室研究氮酮对扑息痛透皮渗透促进作用。     

辅料在各种剂型中的作用

辅料在药物制剂中一般都无药效,但如选用、调配得当,也可起重要作用。不仅能使加工顺利和保证产品质量,且能改进主药的药代动力学作用。本文以辅料所起作用为重点,综述了各类辅料在常规剂型、延效剂型,控释剂型与靶向剂型中应用的理论与实践。     

头孢菌素类抗生素——头孢替坦的研究进展

目的：从原料合成、抗菌活性、体内药动学、适应证、不良反应等方面全面介绍第2代头孢菌素类抗生素——头孢替坦的研究进展,并简略介绍其制剂发展情况,为深入研究提供参考。方法：根椐国内外资料进行分析,归纳,加以综述。结果：头孢替坦是1种半合成长效抗生素,具有广谱抗菌作用,尤其对于革兰阴性菌及厌氧茵作用突出。结论：头孢替坦具有重要的科研和应用价值。     

Comparative investigations on different polymers for the preparation of fast‐dissolving oral films

Objectives The aim was to compare different film‐forming materials used for the preparation of fast‐dissolving oral films. Methods Films were prepared with and without caffeine and caffeine citrate as model drugs. The disintegration/dissolution behaviour of films was investigated using the newly developed slide frame method and Petri dish method. Films were also characterised by dynamic vapour sorption. Key findings All films dissolved within 40 s. Drug‐loaded films disintegrated more slowly than the equivalent drug‐free formulations. Disintegration/dissolution was fastest with films made from the carboxymethyl cellulose C 30 PA 09 (drug‐free < 5 s, drug‐loaded < 10 s). Dissolution times for drug‐loaded oral films made from C 30 PA 09 and HM 6 PA 2910 (hydroxypropyl methyl cellulose) differed significantly (α= 0.05). Dynamic vapour sorption studies revealed higher water absorption ratios for carboxymethyl cellulose films, and these were sticky and difficult to handle. Conclusions This case study showed that hydroxypropyl methyl cellulose was the most suitable film‐forming material for drug‐free and caffeine‐loaded films, providing fast dissolution films that were not sticky and were easy to handle.     

高剂量左氧氟沙星治疗每性细菌霹染的疗效和安全性评价

目的评价高剂量左氧氟沙星治疗常见急性细菌感染的临床疗效和安全性。方法左氧氟沙星500m g,1次/d,分别口服和静脉滴注给药,对呼吸系统、泌尿系统、皮肤软组织的常见细菌感染303例进行临床观察,评价其疗效与安全性。结果口服(148例)与静脉滴注(155例)给药的临床有效率分别为96.62%(143/148)和98.06%(152/155),细菌清除率分别为97.35%(147/151)和98.71%(153/155),平均疗程分别为(4.77±2.12d)和(4.03±1.36d),不良反应发生率分别为6.76%(10/148)和8.39%(13/155)。不良反应多为胃肠道、皮肤反应,且程度轻微,不影响治疗,停药后自然消失。结论左氧氟沙星高剂量(500m g,1次d/)口服或静脉滴注给药疗效高且起效迅速,未见明显严重的不良反应。     

Enhancing the Dissolution Stability of Hard Gelatin Capsules Using Activated Carbon as a Packaging Component

Hard gelatin capsule (HGC) shells are widely used to encapsulate drugs for oral delivery but are vulnerable to gelatin cross-linking, which can lead to slower and more variable in vitro dissolution rates. Adding proteolytic enzymes to the dissolution medium can attenuate these problems, but this complicates dissolution testing and is only permitted by some regulatory authorities. Here, we expand the scope of our previous work to demonstrate that canisters containing activated carbon (AC) or polymeric films embedded with AC particles can be used as packaging components to attenuate gelatin cross-linking and improve the dissolution stability of hard gelatin-encapsulated products under accelerated International Council for Harmonisation conditions. We packaged acetaminophen and diphenhydramine HCl HGCs with or without AC canisters in induction-sealed high-density polyethylene bottles and with or without AC films in stoppered glass vials and stored these samples at 50°C/75% relative humidity through 3 months and at 40°C/75% relative humidity for 6 months. Samples packaged with AC canisters or AC films dissolved more rapidly than samples packaged without AC when differences were observed. These results demonstrate that different sources and formats of AC can enhance the dissolution stability of HGCs packaged in bottles and other potential packaging systems such as blister cards.     

巴中产栀子解热抗炎药理效应研究

目的：探索巴中产栀子对内毒素所致家兔发热模型的解热药理效应及其抑制0．6％冰醋酸所致小鼠腹腔毛细血管通透性增加的抗炎药理效应。方法：针对家兔耳缘静脉注射内毒素生理盐水溶液制备发热模型与0．6％冰醋酸溶液所致小鼠腹腔毛细管通透性增加的炎症模型,分别灌胃给予栀子水溶性有效部位、70％醇溶性有效部位,测定家兔体温、小白鼠腹腔液吸光度值,观察不同产地栀子的解热抗炎作用。结果：巴中产栀子提取水溶性有效部位对发热家兔的降温效果优于江西、湖北、江津产栀子（P〈0．01）;巴中产栀子提取醇溶性有效部位对发热家兔的降温效果明显优于江津和江西栀子70％醇溶性有效部位（P〈0．05或0．01）,与湖北产栀子比较有降低趋势,但差异无统计学意义（P〉0．05）。巴中产栀子有效性部位抑制0．6％冰醋酸所致小鼠腹腔毛细血管通透性增加的效果与江西、湖北、江津产栀子相比,差异无统计学意义（P〉0．05）。结论：巴中产栀子在解热方面的品质更优,疗效更佳。     

利福定不同晶型和制剂的生物利用度

利福定为一多晶型化合物。实验表明由Ⅰ型或Ⅳ型晶型的利福定制成的胶囊剂有较高的生物利用度和疗效。     

Antipyretic analgesics in patients on antiepileptic drug therapy

Summary The effect of administration for three days of acetylsalicylic acid (1500 mg/day), phenylbutazone (300 mg/day), paracetamol (1500 mg/day) and tolfenamic acid (300 mg/day) on serum concentrations of phenytoin and carbamazepine were studied in a group of patients on continuous antiepileptic therapy. When measured 10 h after the last dose of the analgesics, the only significant effect was a decrease in total serum phenytoin after three days of phenylbutazone. When six patients on continuous phenytoin therapy took phenylbutazone for two weeks there was at two days an initial decrease, followed by a significant increase in total serum phenytoin and a concomitant increase in free phenytoin in serum. Even phenylbutazone was well tolerated by most of the patients. However, its use had to be discontinued in one patients due to obvious signs of phenytoin intoxication, with concomitant increases in the serum free and total phenytoin concentrations.     

FDA《根据BCS豁免速释固体口服制剂体内生物利用度和生物等效性研究的指导原则》介绍

美国食品药品管理局于2017年12月发布了《根据生物药剂学分类系统豁免速释固体口服制剂体内生物利用度和生物等效性研究指导原则》的正式版本。该指导原则指出原料药属于生物药剂学分类系统（BCS）1类（而且制剂是速溶的）和3类（而且制剂是极速溶的）的速释（IR）固体口服制剂的生物利用度（BA）或生物等效性（BE）研究可获得豁免。正式版本对2015年草案版做了许多修订。详细介绍该指导原则的正式版本并标明约30处修订。该指导原则对我国IR固体口服制剂BA或BE研究的豁免和监管有重要参考价值。