Bottom-Up and Top-Down Approaches to Explore Sodium Dodecyl Sulfate and Soluplus on the Crystallization Inhibition and Dissolution of Felodipine Extrudates

The objectives of this study were to explore sodium dodecyl sulfate (SDS) and Soluplus on the crystallization inhibition and dissolution of felodipine (FLDP) extrudates by bottom-up and top-down approaches. FLDP extrudates with Soluplus and SDS were prepared by hot melt extrusion, and characterized by polarized light microscopy, differential scanning calorimetry, and fourier transform infrared spectroscopy. Results indicated that Soluplus inhibited FLDP crystallization, and the whole amorphous solid dispersions (ASDs) were binary FLDP-Soluplus (1:3) and ternary FLDP-Soluplus-SDS (1:2:0.15～0.3 and 1:3:0.2～0.4) extrudates. Internal SDS (5%-10%) decreased glass transition temperatures of FLDP-Soluplus-SDS ternary ASDs without presenting molecular interactions with FLDP or Soluplus. The enhanced dissolution rate of binary or ternary Soluplus-rich ASDs in the nonsink condition of 0.05% SDS was achieved. Bottom-up approach indicated that Soluplus was a much stronger crystal inhibitor to the supersaturated FLDP in solutions than SDS. Top-down approach demonstrated that SDS enhanced the dissolution of Soluplus-rich ASDs via wettability and complexation with Soluplus to accelerate the medium uptake and erosion kinetics of extrudates, but induced FLDP recrystallization and resulted in incomplete dissolution of FLDP-rich extrudates. In conclusion, top-down approach is a promising strategy to explore the mechanisms of ASDs' dissolution, and small amount of SDS enhances the dissolution rate of polymer-rich ASDs in the nonsink condition.     

Exploring the feasibility of the use of biopolymers as a carrier in the formulation of amorphous solid dispersions – Part I: Gelatin

Biopolymers have rarely been used so far as carriers in the formulation of amorphous solid dispersions (ASD) to overcome poor solubility of active pharmaceutical ingredients (APIs). In an attempt to enlarge our knowledge on this topic, gelatin, type 50PS was selected. A screening study was initiated in which twelve structurally different poorly soluble biopharmaceutical classification system (BCS) Class II drugs (carbamazepine, cinnarizine, diazepam, itraconazole, nifedipine, indomethacin, darunavir (ethanolate), ritonavir, fenofibrate, griseofulvin, ketoconazole and naproxen) were selected for evaluation. Solid dispersions of five different drug loadings of these twelve compounds were prepared by lyophilization and evaluated for their solid state properties by mDSC and XR(P)D, and in vitro dissolution performance. Even without any process optimization it was possible to form either fully amorphous or partially amorphous systems, depending on the API and API to carrier ratio. Hence in this respect, gelatin 50PS behaves as any other carrier. Dissolution of the API from the solid dispersions significantly exceeded that of their crystalline counterparts. This study shows the potential of gelatin as a carrier to formulate amorphous solid dispersions.     

头孢丙烯与头孢克洛随机对照治疗下呼吸道感染患者的临床评价

目的　评价头孢丙烯与头孢克洛随机对照治疗下呼吸道感染的疗效和安全性。方法　轻、中度下呼吸道感染患者 12 0例随机分成两组 ,头孢丙烯组 6 2例予头孢丙烯 5 0 0mg ,口服 ,2次 /d ;头孢克洛组 5 8例予头孢克洛5 0 0mg ,口服 ,3次 /d。两组均以 7～ 14天为 1个疗程。结果　头孢丙烯组与头孢克洛组的临床有效率分别为 91.9%与 89.7% (P >0 .0 5 ) ,细菌消除率为 89.8%与 88.9% (P >0 .0 5 ) ,两组均无明显不良反应。结论　头孢丙烯可作为治疗轻、中度下呼吸道感染有效和安全的抗生素     

头孢丙烯治疗下呼吸道细菌性感染的临床评价

目的：评价头孢丙烯治疗下呼吸道细菌性感染的有效性和安全性。方法：采用随机对照开放试验方法。选用头孢呋辛片为对照药，共治疗下呼吸道细菌感染81例，头孢丙烯组40例，500mg；头孢呋辛组41例，500mg，均为每日两次，疗程7－14d。结果：头孢丙烯组及头孢呋辛组有效率分别为90．0％和80．5％，细菌阳性病例有效率分别为82．1％，和72．4％，本试验共分离致病菌57析，细菌清除率分别为82．1％和75．9％，安全性评价分别为41例和43例，不良反应发生率分别为7．3％和9．3％，经统计学处理差异无显著性（P＞0．05），结论：采用头孢丙烯治疗急性下呼吸道细菌感染安全，有效。     

浅谈国外客户对原料药的质量审计

目的 浅析国外客户对原料药的质量审计.方法 介绍了质量审计的目的和特点,并针对客户审计的重点,按审计过程进行详细论述和分析.结果与结论 在准备和接受国外客户质量审计的活动中,完善了自身的质量管理体系,提高了企业的产品质量水平和国际市场竞争力.     

头孢丙烯微生物限度检查方法的验证

目的 建立头孢丙烯原料的微生物限度检查方法,并对其进行方法学验证。方法 按中国药典2010年版方法对3 个批号的头孢丙烯原料进行微生物限度检查方法验证。细菌的计数方法和控制菌检查均采用低速离心-薄膜过滤-酶中和联用法;霉菌和酵母菌计数采用平皿法。结果 各试验菌的回收率均高于70%,稀释液回收率也均高于70%,控制菌检查具有专属性,满足中国药典2010 版验证试验的要求。结论 本品的微生物限度检查方法有效可行,可用于头孢丙烯原料的微生物限度检查。     

Comparison of Trimethoprim-Sulfamethoxazole,Cephadroxil and Cefprozil as Prophylaxis for Recurrent Urinary Tract Infections in Children

Abstract

The aim of this study was to compare the efficacy of prophylactic trimethoprimsulfamethoxazole (TMP/SMZ), cefprozil and cephadroxil treatments in children who have recurrent urinary tract infection, but no urinary tract pathology. After acute urinary tract infections (UTIs) were treated, the patients were divided into 3 groupsrandomly and TMP/SMZ was given to 21 patients, cephadroxil was given to 25 patients and cefprozil was given to 34 patients for 3 months—one dose at night. All patients were followed for 6 months following prophylaxis. The frequency of symptomatic UTIs among groups during prophylaxis was not statistically different, however the number of symptomatic UTIs in the cephadroxil group was lower than the other groups. Asymptomatic bacteriuria episodes were detected in TMP/SMZ and cefprozil groups, whereas no asymptomatic bacteriuria episodes were seen in the cephadroxil group. The number of patients with symptomatic UTI during the follow-up period was not different between groups, however all the asymptomatic bacteriuria episodes were encountered in the cefprozil group. In conclusion, in this study cephadroxil was found to be slightly superior to TMP/SMZ and cefprozil in preventing asymptomatic bacteriuria episodes and symptomatic UTIs in children with recurrent UTI and normal urinary tract system.     

头孢丙烯治疗小儿急性呼吸道感染疗效观察

目的评价头孢丙烯治疗小儿急性呼吸道感染的临床疗效及安全性。方法将轻、中度急性呼吸道感染患儿180例随机分成两组,头孢丙烯组90例,给予头孢丙烯15mg／（kg·d）,口服,2次,头孢克洛组90例,给予头孢克洛20mg／（kg·d）,口服,3次,两组疗程均为7-10d。结果头孢丙烯组与头孢克洛组临床有效率分别为90.24％与85.00％（P〉0.05）,两组比较差异无统计学意义。两组均元明显不良反应。结论头孢丙烯治疗小儿轻、中度急性呼吸道感染疗效确切且安全。     

头孢丙烯在下呼吸道细菌感染患者的药代动力学研究

目的:通过研究下呼吸道细菌感染患者的头孢丙烯临床药代动力学参数,为临床选择合理给药方案提供依据。方法:用HPLC法测定10例下呼吸道细菌感染患者连续给药5d后的稳态血药浓度,数据用3P97 药物动力学模拟系统处理。结果:头孢丙烯的药时曲线符合二室开放模型,主要药代动力学参数:t1/2为 (1．55±0．17)h,MRT为(2．52±0．15)h,Cmax为(13．32±1．28)μg／mL,tmax为(1．41±0．31)h,AUC0-10为 (31．68±7．68)μg h／mL。结论:口服头孢丙烯片500mg,每天2次,能获得控制下呼吸道细菌感染的有效治疗浓度。     

头孢丙烯的合成

以7-苯乙酰胺基-3-氯甲基-3-头孢烯-4-羧酸二苯甲酯为起始原料,经7-位酰胺基水解、在DCC作用下与侧链D-2-叔丁氧羰基氨基-2-(4-羟苯基)乙酸缩合、3-位氯甲基置换为碘甲基后与三苯膦成内鎓盐,与乙醛进行Wittig反应在3-位形成丙烯基,最后在三氟乙酸作用下脱去7-位侧链氨基和4-位羧基的保护基制得头孢丙烯,总收率16.4%.