氟喹诺酮类药物的无菌检查方法验证

目的完善氟喹诺酮类药物注射剂的无菌检验方法标准。方法通过确定冲洗量、选择阳性对照菌及加入顺序等,以8种氟喹诺酮类注射液为例,说明无菌检查法建立在验证试验基础上的必要性。结果乳酸环丙沙星、乳酸左氧氟沙星、盐酸洛美沙星、加替沙星、甲磺酸培氟沙星、氟罗沙星、卡曲沙星等8种注射液的验证试验,保证无菌检查条件,证明方法可行。结论建议将验证方法收载入中国药典。     

注射用加替沙星的制备及质量控制

目的：建立加替沙星注射液的制备和质量控制方法。方法：确定注射剂的配置工艺，以HPLC法测定加替沙星的含量，进行稳定性考察。结果：本品制剂质量稳定，用HPLC法测定含量，平均回收率100．3％，重复性试验RSD为1．75％。结论：制备工艺可行，质量稳定，质量控制方法可靠。     

盐酸加替沙星片剂与乳酸左氧氟沙星片剂随机双盲对照治疗急性细菌性感染临床研究

目的评价国产盐酸加替沙星片剂治疗急性细菌性呼吸道感染与泌尿道感染的有效性和安全性。方法采用区组随机化、双盲、平行对照临床试验设计，试验药盐酸加替沙星与对照药乳酸左氧氟沙星片剂用法均为每次200mg。一日2次。疗程均为7～14d。结果本试验共入选74例，因各种原因淘汰12例，最终列入疗效评价的病例数为62例，盐酸加替沙星组32例，乳酸左氧氟沙星组30例。治疗结束后盐酸加替沙星与乳酸左氧氟沙星痊愈率分别为75．0％与73．3％。有效率分别为93．8％与90．0%，细菌清除率分别为86．7％与88．5％；在试验期间，盐酸加替沙星组有1例发生皮疹，乳酸左氧氟沙星组有2例发生不良反应（1例转氨酶升高，1例恶心、食欲差）；上述结果经统计学检验无显著性差异。结论盐酸加替沙星与乳酸左氧氟沙星片剂治疗临床常见细菌性呼吸道、泌尿道感染均有效、安全。     

盐酸氨溴索注射液与注射用加替沙星的配伍稳定性考察

目的：考察25℃与37℃下,盐酸氨溴索注射液与注射用加替沙星在0．9％氯化钠注射液中的配伍稳定性。方法：采用RP-HPLC-二极管阵列检测器测定盐酸氨溴索与加替沙星在0．9％氯化钠注射液中配伍后8h内各时间段的含量,同时测定pH,观察配伍液的外观变化。结果：在25℃与37℃下、8h内,配伍液外观、pH及含量均无明显变化。结论：盐酸氨溴索注射液与注射用加替沙星在0．9％氯化钠注射液中8h,pH、外观、含量基本无变化,微粒检测等尚有待进一步试验。     

注射用阿奇霉素的成盐剂的研究

目的选择适合的注射用阿奇霉素成盐剂。方法将阿奇霉素与8种酸制成溶液及冻干粉针剂，并通过对pH值、初步稳定性试验及在动物体内静脉滴注阿奇霉素与8种盐冻干制剂，比较其肝脏毒性，选择适当的成盐剂。结果谷氨酸、乳糖酸、酒石酸和天冬氨酸与阿奇霉素的盐溶液较为稳定且pH值属于合适范围；动物试验显示各参比盐制剂病理结果均有不同程度的改变，表现较轻者有谷氨酸盐、柠檬酸盐、天冬氨酸盐、硫酸盐、盐酸盐，较重者有磷酸二氢盐、乳糖酸盐、酒石酸盐。结论谷氨酸、天冬氨酸均为合适的阿奇霉素成盐剂。     

加替沙星注射液的制备及HPLC法含量测定

目的探讨加替沙星注射液的处方、制备工艺和含量测定方法。方法以乳酸为增溶剂及pH值调节剂制备加替沙星注射液；用HPLC法测定本品的含量。结果制备的加替沙星注射液在冷藏(2℃～4℃)、高温(60℃)、光照(30001x)下及配制过程中含量稳定，除碳酸氢钠外与大部分常用输液可配伍使用。结论处方合理，工艺可行，制备的注射液性质稳定，含量测定方法准确可靠。     

2009年国产加替沙星注射剂评价性抽验结果及质量评价

目的:评价国产加替沙星注射剂的质量现状及存在问题。方法:按照2009年度国家评价性抽验计划总体要求,采用法定检验方法结合探索性研究进行样品检验,统计分析检验结果对国产加替沙星注射剂的质量现状进行评价。结果:法定检验显示70批样品中69批合格,有1批因可见异物不合格;探索性研究显示部分生产企业产品的渗透压测定结果明显低于各国药典规定的限度规定,而采用HPLC法分析了加替沙星注射剂和原料中杂质的分布情况,结果表明注射液中的杂质主要源于原料;对不同生产工艺的加替沙星注射液的光照稳定性进行了比较,结果表明如生产中以稀盐酸代替乳酸助溶,加替沙星注射剂的光稳定性更好。结论:加替沙星注射剂按各执行标准检验,总体合格率较好。但是还存在一些问题,如细菌内毒素限度需要规范统一、100℃30 min灭菌工艺能否保障无菌等。通过探索性研究还建议生产企业改进生产工艺,提高产品质量;同时改进并统一现行质量标准,进一步加强对加替沙星注射剂的监管。     

复方盐酸普鲁卡因注射液的研制及药效学

目的：研制一种复方盐酸普鲁卡因注射液以解决单方普鲁卡因注射液存在的缺点和不足。方法：将盐酸普鲁卡因与盐酸利多卡因配伍制成复方制剂，经急性毒性试验，以确保临床用药安全，再通过复方盐酸普鲁卡因注射液对蟾蜍神经动作电位的影响以确定其药效。结果：复方盐酸普鲁卡因注射液药效均强于相同浓度的盐酸普鲁卡因与盐酸利多卡因。结论：复方盐酸普鲁卡因注射液毒性低，用药安全范围大，弥补了单方盐酸普鲁卡因注射液的缺点和不足。     

注射用加替沙星与常用输液的配伍稳定性

目的考察加替沙星与常用输液配伍的稳定性。方法利用高效液相色谱法，测定注射用加替沙星在5％葡萄糖注射液和0.9％氯化钠注射液中，于4℃、25℃和37℃，不同时间段内溶液的颜色、pH值和加替沙星浓度的变化。结果不同条件下加替沙星注射剂与常用输液配伍后溶液的颜色、pH值、加替沙星浓度基本不变，认为注射用加替沙星在氯化钠溶液和葡萄糖溶液中24h内稳定。结论加替沙星注射剂可以与氯化钠输液和葡萄糖输液配伍应用。     

加替沙星治疗老年细菌性下呼吸道感染的临床疗效评价

目的：评价加替沙星注射剂治疗下呼吸道感染的临床疗效与安全性。方法：以头孢哌酮钠-舒巴坦钠注射液为对照药，在156例受试患者中进行随机平行对照试验。治疗组85例，给予加替沙星注射液0．4g，静脉滴注，qd；对照组71例，给予头孢哌酮钠-舒巴坦钠注射液2g静脉滴注，bid，疗程均为7d。结果：治疗组和对照组的有效率分别为91．76％和92．96％；治疗组细菌清除率为92．65％，略高于对照组的89．23％；不良反应发生率分别为5．88％和4．6％。两组间的差异无显著性（P〉0．05）。结论：加替沙星注射剂治疗临床常见致病茵引起的下呼吸道感染，疗效好，使用安全，有临床应用价值。     

混合痔切除术后4种用药方案的成本-效果分析

目的:评价混合痔切除术后4种用药方案的经济效果。方法:运用药物经济学原理对(A)乳酸左氧氟沙星 奥硝唑 注射用七叶皂苷钠(、B)加替沙星 奥硝唑(、C)甲磺酸左氧氟沙星 奥硝唑 头孢羟氨苄、(D)盐酸左氧氟沙星 诺氟沙星4种用药方案的成本-效果进行分析。结果:总有效率各组间差异无显著性,A、B、C、D组成本-效果比分别为45.86、38.50、36.11、26.53。A、B、C组相对于D组的增量成本-效果比分别为299.84、353.19、-208.36。结论:D组方案为较佳方案。     

Effect of chloride ion on dissolution of different salt forms of haloperidol, a model basic drug

The effect of chloride ion (Cl-) on dissolution rates of hydrochloride, mesylate (methanesulfonate) and phosphate salt forms of a model drug, haloperidol, was investigated. The dissolution rates of the salts in 0.01 M HCl from rotating disks followed the order of mesylate>phosphate>hydrochloride. With additional chloride ion, a decrease in dissolution rate of the hydrochloride salt was observed due to the common ion effect. Dissolution rates of mesylate and phosphate salts also decreased due to their conversion to the HCl salt form on the surfaces of dissolving disks, however, the dissolution rates of mesylate and phosphate salts under identical chloride ion concentrations were still higher than that of the HCl salt. In powder dissolution studies, it was observed that kinetics of nonhydrochloride-to-hydrochloride salt conversion play a major role in dissolution; the mesylate dissolved completely (<5 min) before its dissolution rate could be impeded by its conversion to the hydrochloride salt form. Therefore, despite the potential for conversion to a hydrochloride salt form, certain nonhydrochloride salt forms may still be preferred for dosage form development due to kinetic advantages during dissolution, such as higher apparent dissolution rate of a nonhydrochloride salt before it could completely convert to the hydrochloride form.     

注射用甲磺酸加替沙星细菌内毒素检查法研究

目的建立注射用甲磺酸加替沙星细菌内毒素检测方法。方法用不同厂家的鲎试剂对不同批号的注射用甲磺酸加替沙星分别进行干扰试验,考察确立注射用甲磺酸加替沙星细菌内毒素检测方法。结果注射用甲磺酸加替沙星稀释液500μg.mL-1、83.3μg.mL-1对细菌内毒素检测无干扰。结论注射用甲磺酸加替沙星可用细菌内毒素检查方法取代家兔热原检查法。     

酒石酸布托啡诺、盐酸曲马多及昂丹司琼注射剂体外配伍稳定性考察

目的:考察酒石酸布托啡诺注射液、盐酸曲马多注射液及盐酸昂丹司琼注射液在0.9%氯化钠注射液中的配伍稳定性。方法:采用HPLC法测定配伍液中三种药物含量,考察三种药物在0.9%氯化钠注射液中,室温条件下72 h内的含量变化,同时观察与检测外观与pH变化。结果:酒石酸布托啡诺注射液、盐酸曲马多注射液及盐酸昂丹司琼注射液的配伍液在72 h内三种药物含量未见明显变化,配伍液外观澄清,pH值保持稳定。结论:酒石酸布托啡诺、盐酸曲马多及盐酸昂丹司琼在0.9%氯化钠注射液中室温条件下、72 h内保持稳定。     

甲磺酸加替沙星片在健康志愿者体内的药动学

目的 :研究健康志愿者口服甲磺酸加替沙星片后的药动学特征 ,为临床安全、合理用药提供参考依据。方法 :18名健康男性单剂量口服甲磺酸加替沙星片 4 0 0mg ,以高效液相色谱法测定服药后 2 4h内的血药浓度 ,计算其药动学参数。结果 :甲磺酸加替沙星片在健康人体内的处置符合一级吸收的一室代谢模型 ,主要药动学参数Tmax,Cmax,T12 β,AUC( 0 2 4 ) 分别为 :(1.5±s 0 .4 )h ,(3.4± 1.0 )mg·L- 1,(6 .6± 1.0 )h ,(33± 10 )mg·h·L- 1。结论 :甲磺酸加替沙星在人体内的药动学特征与文献报道的盐酸加替沙星相似 ,口服吸收快 ,生物利用度高、体内平均滞留时间长 ,且存在个体差异。     

丙泊酚的配伍研究

目的:考察室温下2h内,静安乳剂分别与乳酸钠林格注射液、盐酸氯胺酮注射掖及盐酸普鲁卡因注射液配伍的稳定性.方法:采用离心分光光度法、苏丹染色实验、电导率测定以及混合液pH值和丙泊酚含量的测定等方法来考察静安乳剂与其他注射液配伍后的稳定性.结果:室温下2h内静安乳剂与乳酸钠林格注射液或盐酸普鲁卡因注射液配伍后的稳定性要优于与盐酸氯胺酮注射液的配伍.结论:静安乳剂与上述三种注射液配伍后,具有一定的稳定性,为了进一步证实配伍后混合液的安全性,还有必要进一步研究,特别是分解产物与相关物质的分析研究.     

Investigation of Solubility and Dissolution of a Free Base and Two Different Salt Forms as a Function of pH

No HeadingPurpose. To evaluate the effect of pH on solubility and dissolution rates of a model weak base, haloperidol, and two different salt forms, hydrochloride and mesylate.Methods. pH-solubility profiles were determined by using haloperidol base, haloperidol hydrochloride, and haloperidol mesylate as starting materials; concentrated or diluted HCl or NaOH solutions were added to aqueous suspensions of solids to adjust pH to desired values. Intrinsic dissolution rates were determined using intrinsic dissolution apparatus under various pH-stat conditions. Further, approximation of diffusion layer pH was estimated from that of 10% w/w slurries of drug substances in dissolution media, which were used to correlate with intrinsic dissolution rates of haloperidol and its salt forms under different pHs.Results. pH-solubility profiles of haloperidol base and its HCl salt were similar, while when the mesylate salt was used as starting material, it exhibited a higher solubility between pH 2 and 5. The higher solubility of the mesylate salt at pH 2–5 is attributed to its higher solubility product (K_sp) than that of the hydrochloride salt. The pH-solubility profiles indicated a pH_max (pH of maximum solubility) of 5, indicating that the free base would exist as the solid phase above this pH and a salt would be formed below this pH. Below pH 1.5, all solubilities were comparable due to a conversion of haloperidol base or the mesylate salt to the HCl salt form when HCl was used as the acidifying agent. These were confirmed by monitoring the solid phase by differential scanning calorimeter. When their dissolution rates are tested, dissolution rates of the mesylate salt were much higher than those of the free base or the HCl salt, except at very low pH (<2). Dissolution rates of free base and HCl salt also differed from each other, where that of HCl salt exhibits higher dissolution rates at higher pHs. A direct correlation of dissolution rate with solubility at diffusion layer pH at the surface of dissolving solid was established for haloperidol, its hydrochloride, and mesylate salts.Conclusions. Using pH-solubility and pH-dissolution rate interrelationships, it has been established that diffusion layer pH could be used to explain the observed rank order in dissolution rates for different salt forms. A non-hydrochloride salt, such as a mesylate salt, may provide advantages over a hydrochloride salt due to its high solubility and lack of common ion effect unless at very low pH.     

多索茶碱、甲磺酸酚妥拉明及盐酸多巴胺注射液的配伍稳定性

目的：考察多索茶碱注射液、甲磺酸酚妥拉明注射液及盐酸多巴胺注射液的配伍稳定性。方法：观察及测定3种注射液在0．9％氯化钠注射液和5％葡萄糖注射液中配伍后于室温放置24h内的外观、pH及不溶性微粒,并采用高效液相色谱法测定配伍液中3种主药的含量。结果：多巴胺及酚妥拉明不影响多索茶碱的稳定性,配伍液pH对甲磺酸酚妥拉明、盐酸多巴胺的稳定性影响较大。结论：多索茶碱注射液、甲磺酸酚妥拉明注射液及盐酸多巴胺注射液适以5％葡萄糖注射液作溶媒配伍于24h内使用,不宜与0．9％氯化钠注射液配伍使用。     

Preparation and characterization of salt forms of enalapril

Selection of an optimal salt form of a drug candidate is a vital component of preformulation stage of drug development. In this study, six salts of enalapril--citrate, mesylate, tartrate, malate, besylate and tosylate--were prepared and characterized by Mass Spectroscopy, Differential Scanning Calorimetry, Thermogravimetric Analysis, Microscopy, Powder X-ray Diffraction, Karl Fischer Titration, High Performance Liquid Chromatography, Fourier-Transform Infra-red Spectroscopy and Head Space Gas Chromatography. All the six salts were subjected to a tiered screening involving five stages in the following order: crystallinity, hygroscopicity, solubility, stability and flow/compactability. Enalapril malate showed encouraging profile because of its lower hygroscopicity, higher solubility, good solid state stability, and better flow and compactability, in comparison to the marketed maleate salt.