头孢泊肟酯分散片的制备及溶出度测定

目的制备头孢泊肟酯分散片并建立其溶出度测定方法。方法以可压性、崩解时限、分散均匀性、溶出度为主要评价指标确定最终最佳处方;采用中国药典2005年版二部附录ΧC溶出度测定第一法,以0.05 mol.L^-1盐酸为溶出介质,转速为100 r.min-1,在第30 min取样,264 nm波长处测定其溶出度。结果最终处方为头孢泊肟酯43.3%,羧甲基淀粉钠21.7%,微晶纤维素10%,羟丙基纤维素10%,交联聚维酮4.33%,十二烷基硫酸钠0.67%,微粉硅胶5%,阿斯巴甜3.33%,桔子香精1.67%。头孢泊肟酯溶出度检测浓度的线性范围为6.25-31.25μg.mL-1（r2=0.999 6）;平均回收率为99.66%,RSD=0.5%（n=9）,6批样品30 min溶出度均＆gt;85%。与日本三共株式会社生产的头孢泊肟酯片相比,分散片前30 min的溶出速度快于普通片剂。结论头孢泊肟酯分散片制备工艺简单;溶出度测定方法操作简便、结果准确。     

头孢克肟颗粒溶出度检查方法研究

目的建立头孢克肟颗粒中主药溶出度的测定方法。方法采用紫外分光光度法．在288nm波长处测定头抱克肟颗粒中主药的吸收度。并计算回收率和溶出度。结果头抱克肟检测浓度线性范围为2．67～21．36μg·mL^-1（r=0．9990）;平均回收率为99．9％（RSD=0.70％,n=9）;3批样品在45min溶出量均在75％以上。结论本方法准确、可靠。可用于该制剂的溶出度测定。     

头孢泊肟匹酯片溶出度测定方法

本文建立了头孢泊肟匹酯片溶出度测定方法。以盐酸溶液 (9→ 10 0 0 )为溶剂 ,转速 10 0 r/ min,采用紫外分光光度法测定头孢泊肟匹酯片溶出量 ,测定波长为 2 6 3nm。线性浓度范围 3～ 2 4μg/ ml,r=0 .9999。经 30 min取样 ,三批头孢泊肟匹酯片的溶出量均大于 90 %。方法简便、准确 ,重复性好     

头孢泊肟酯片溶出度方法研究

目的:考察国内12个生产企业62批头孢泊肟酯片的溶出度情况,对其现行方法的合理性与有效性进行评价。方法：分别采用《中国药典》2010年版、USP 35与JP16所收载方法测定头孢泊肟酯片的累积溶出量。结果：采用《中国药典》的方法检查,国内12个生产企业的62批样品溶出度合格率为100%,而采用《美国药典》与《日本药局方》的方法测定,合格率仅分别为40.3%与30.7%;大部分生产企业的样品的3条累积溶出曲线与国外原研制剂相差较大。结论：头孢泊肟酯片现行标准中的溶出度检查方法不能很好的区分不同处方的产品质量,同时,根据头孢泊肟酯制剂需饭后服用的要求（餐后胃液pH值为3.5）,该溶出介质也不能合理地反映产品在体内的真实溶出状况,建议对该检验方法进行修订。     

头孢泊肟酯高效液相色谱含量测定方法的改进

目的:改进以高效液相色谱法测定头孢泊肟酯及其制剂含量的方法。方法:色谱柱为C18,流动相为甲醇-水(50∶50),流速为1.5mL.min-1,柱温为40℃,检测波长为235nm。结果:头孢泊肟酯的线性范围为25～150μg.mL-1(r=0.9999);平均回收率为98.56%(RSD=1.79%),样品平均含量为101.54%。结论:本方法简便、快速、准确、灵敏,可用于头孢泊肟酯及其制剂的含量测定。     

高效液相色谱法测定头孢克肟颗粒的溶出度

目的采用高效液相色谱(HPLC)法测定头孢克肟颗粒的溶出度。方法采用Waters Sunfire C18色谱柱(4.6 mm×250 mm,5μm);流动相为四丁基氢氧化铵溶液(取10%四丁基氢氧化铵溶液25 mL,加水1 000 mL,摇匀,用1.5 mol·L-1磷酸溶液调节pH至7.0)-乙腈(72∶28);检测波长288 nm;进样量20μL。结果头孢克肟在8～160μg·mL-1范围内呈良好线性关系,r=0.999 9,平均回收率为99.67%,RSD为0.56%(n=9)。结论该方法简单,能准确测定头孢克肟颗粒的溶出度,专属性良好。     

高效液相色谱法测定头孢泊肟酯含量的方法学研究

目的对头孢泊肟酯及其制剂含量的高效液相色谱检测法进行改进,并与紫外分光光度法作比较。方法以ODS-C18为固定相,甲醇-水(50∶50)为流动相,流速为1.5 mL.min-1,柱温为40℃,检测波长235 nm。结果头孢泊肟酯的浓度在25~150μg.mL-1内线性关系良好,回归方程为:A=7.457C-1.1287,r=0.999 9(n=7),测定头孢泊肟酯胶囊含量重复性良好,RSD为1%(n=9)。头孢泊肟酯胶囊的平均回收率为98.56%,平均含量为101.54%。结论本法简便、快速、准确、灵敏,可用于头孢泊肟酯及其制剂的含量测定。     

4种头孢泊肟酯片的体外溶出度比较

目的考察4种市售头孢泊肟酯片的体外溶出度，评价其片剂质量。方法采用《中华人民共和国药典》(2000年版)溶出度测定法第2法，以盐酸溶液(9→1 000)为溶剂，转速分别为100和50 r·min^-1，进行溶出度测定实验。采用紫外分光光度法测定溶出量，测定波长为263 nm。计算累积溶出率。结果 线性范围为3～18 μg·mL^-1，r＝ 0.999 6。45 min内4种待测药物在盐酸溶液(9→1 000)中的累积溶出百分率均＞70.0%。转速为100 r·min^-1时，4种头孢泊肟酯片30 min溶出率均＞90.0%；转速为50 r·min^-1时，4种头孢泊肟酯片45 min内的溶出率均＞70.0%。结论4种被测头孢泊肟酯片均符合质量标准，但不同生产厂家的产品之间有差异。     

乙酰吉他霉素颗粒溶出度检查方法研究

目的建立乙酰吉他霉素颗粒中主药溶出度的测定方法。方法采用紫外分光光度法,在231 nm波长处测定乙酰吉他霉素颗粒中主药的吸收度,并计算回收率和溶出度。结果乙酰吉他霉素检测浓度线性范围为5.230-41.84 mg·L^-1（r=0.9999）;平均回收率为99.9%（RSD=0.37%,n=9）;三批样品在45 min溶出量均在75%以上。结论本方法准确、可靠,可用于该制剂的溶出度测定。     

HPLC法测定人血浆中头孢泊肟的浓度

目的建立测定人血浆中头孢泊肟酯的活性代谢产物头孢泊肟浓度的高效液相色谱法,并应用于头孢泊肟酯干混悬剂在健康人体内的药动学研究。方法采用沉淀蛋白法进行样品预处理,色谱柱为Agilent Zorbax SB-C18柱(150 mm×4.6 mm,5μm),流动相为乙腈-20 mmol.L-1磷酸二氢铵缓冲液(体积比为9∶91,含6.6 mmol.L-1三乙胺,磷酸调pH值至2.0),流速为1.0 mL.min-1,检测波长为254 nm,内标为头孢克洛。结果头孢泊肟浓度线性范围为0.102～6.528 mg.L-1,低、中、高3个质量浓度的提取回收率分别为92.0%、93.3%和92.1%,日内和日间精密度RSD(n=6)分别为3.3%、3.8%、2.0%和14.2%、2.9%、6.3%。头孢泊肟血浆样品室温放置2 h、预处理后室温放置24 h、经历1次及3次冷冻-解冻循环和-20℃冷冻情况下保存40 d均可保持稳定。结论此法适用于头孢泊肟酯药动学研究。     

头孢泊肟酯分散片的处方筛选及稳定性研究

目的:筛选头孢泊肟酯分散片最佳处方并评价制剂稳定性。方法:通过正交试验设计处方,以溶出度、崩解时限及混悬液稳定性为评价指标确定最佳处方;与普通片进行体外溶出度比较,并在不同条件下留样进行稳定性研究。结果:最佳处方为各辅料用量预胶化淀粉40%,交联聚乙烯吡咯烷酮XL10%,十二烷基硫酸钠0.5%,微粉硅胶10%,由此制得的片剂外观光洁,崩解迅速,几乎在30s内崩解完全,并能通过内径为710μm的筛;分散片溶出速度快于普通片剂,稳定性好。结论:崩解剂的用量、润湿剂的用量等因素对头孢泊肟酯分散片的性质有明显影响,混悬液稳定性受辅料影响较大,成品有效期为2y。     

4种头孢泊肟匹酯片的体外溶出度比较

目的考察4种头孢泊肟匹酯片的体外溶出度，评价其片剂质量。方法采用2005年版《中国药典（二部）》溶出度测定法第2法。以盐酸溶液（9—1000）为溶出介质，转速为100r／min，用紫外分光光度法测定溶出量（测定波长为263nm），计算累积溶出量。结果在45mi。内不同厂家的待测药物累积溶出量均〉70％。结论4种头孢泊肟匹酯片均符合质量标准，但不同厂家的产品质量还是存在很大的差异。     

Preparation & characterization of solid inclusion complex of cefpodoxime proxetil with beta-cyclodextrin

Cefpodoxime proxetil (CPDX-PR) is an oral cephalosporin antibiotic with poor aqueous solubility and bioavailability. Effect of beta-cyclodextrin on aqueous solubility and dissolution rate of cefpodoxime proxetil was evaluated by the formation of solid inclusion complexes in 1:2 molar ratio of drug: cyclodextrin. Phase solubility study was carried out whereby a typical B's type curve was obtained thus, indicating a 1:2 stoichiometric ratio for optimum complex formation. Solid inclusion complexes in 1:2 molar ratios were prepared by using methods such as physical mixture, solvent evaporation and freeze drying. Prepared complexes were characterized by fourier transform infrared spectroscopy (FT-IR) differential scanning calorimetry (DSC), powder x-ray diffraction (PXRD) and scanning electron microscopy (SEM). Results of in vitro studies appraised of an increased solubility and dissolution rate of cefpodoxime proxetil on complexation with beta- cyclodextrin (P < 0.05) as compared to CPDX-PR alone. Amongst the complexes prepared by different methods, the complex prepared by freeze drying showed the highest dissolution rate (P< 0.01). The in vitro antimicrobial activity of cefpodoxime proxetil and its freeze dried complex (1:2) was studied against both antibiotic-susceptible and antibiotic-resistant clinical isolates of Neisseria gonorrhoeae. The freeze dried complex (1:2) inhibited all penicillin-susceptible strains and penicillinase-producing strains at 0.015 microg/ml concentration. Chromosomally resistant strains which were not responsive to penicillin were inhibited by the complex at 0.125 microg/ml concentration. The study revealed that complexation of cefpodoxime proxetil with beta-cyclodextrin effectively enhanced the aqueous solubility and in vitro antibacterial activity.     

The bioavailability of cefpodoxime proxetil tablets relative to an oral solution

The bioavailability of cefpodoxime proxetil tablets relative to an oral solution of cefpodoxime proxetil in a sucrose/alcohol/citric acid vehicle was studied in 11 healthy volunteers in a randomized, crossover study. Fasted subjects took one cefpodoxime proxetil 100 mg tablet or 50 mL of a 2 mg mL^?1 cefpodoxime proxetil oral solution on two separate occasions. In a third study period, all subjects took a 100 mg dose of the oral solution with a high-fat meal to investigate the effect of food on cefpodoxime proxetil absorption from the oral solution. Serial blood samples were obtained over a 24h period, and urine was collected for 48h after dosing. Cefpodoxime concentrations in plasma and in urine were determined using HPLC methods. The bioavailability of cefpodoxime proxetil tablets relative to the oral solution was 82%, as determined from AUC ratios. There was no difference in the rate of cefpodoxime absorption between dosage forms. Food had no effect on the extent of drug absorption from the oral solution but did result in delayed absorption. These results suggest that complete dissolution of cefpodoxime proxetil is critical for optimal bioavailability.     

Development and Validation of RP-HPLC Method for Simultaneous Estimation of Cefpodoxime Proxetil and Dicloxacillin Sodium in Tablets

A simple, accurate, rapid and precise reversed-phase high-performance liquid chromatographic method has been developed and validated for simultaneous determination of cefpodoxime proxetil and dicloxacillin sodium in tablet. The chromatographic separation was carried out on kromasil C₁₈ analytical column (250×4.6 mm; 5 μm) with a mixture of acetonitrile:methanol:trifloroacetic acid (0.001%) with pH 6.5 (30:50:20, v/v/v) as mobile phase; at a flow rate of 1.0 ml/min. UV detection was performed at 235 nm. The dicloxacillin sodium and cefpodoxime proxetil were eluted at 1.92 and 3.35 min, respectively. The peaks were eluted with better resolution. Calibration plots were linear over the concentration range 0.5-20 μg/ml for cefpodoxime proxetil (r²=0.9996) and 5-50 μg/ml for dicloxacillin sodium (r²=0.9987). The method was validated for accuracy, precision, linearity and specificity. The method was very sensitive with limit of detection 0.0726, 0.3685 μg/ml and limit of quantification 0.220, 1.116 μg/ml for cefpodoxime proxetil and dicloxacillin sodium, respectively. The high recovery and low relative standard deviation confirm the suitability of the method for routine determination of cefpodoxime proxetil and dicloxacillin sodium in bulk drug and tablet dosage form.     

头孢泊肟酯片治疗急性细菌性感染158例的多中心随机对照研究

目的 :评价国产头孢泊肟酯片治疗急性细菌性感染的有效性和安全性。方法 :采用多中心、随机对照研究方法 ,以进口头孢泊肟酯片为对照 ,2组的用量、用法及疗程均为 10 0mg ,po ,bid ,疗程 7～14d。结果 :本研究共入组 175例病人 ,可进行临床疗效评价分析的病例 15 8例 ,试验组 77例 ,对照组81例。试验组总痊愈率和有效率分别为 70 %和92 % ;对照组总痊愈率和有效率分别为 79%和94 % ,2组细菌清除率分别为 98%和 98% ,2组比较差异均无显著意义 (P >0 .0 5 )。试验组和对照组的不良反应发生率分别为 9%和 2 % ,主要表现为口干、恶心、腹部不适及转氨酶增高等。结论 :国产头孢泊肟酯片治疗急性细菌性感染临床疗效确切 ,安全性较好。     

头孢泊肟酯片和颗粒人体相对生物等效性试验研究

目的研究国产头孢泊肟酯片及颗粒与进口头孢泊肟酯片在24名男性健康志愿者体内的生物等效性。方法采用标准3制剂、3周期的二重3×3拉丁方式自身对照试验设计,24例男性健康志愿受试者单剂量口服国产头孢泊肟酯颗粒（受试制剂A）、头孢泊肟酯片（受试制剂B）和进口头孢泊肟酯片（参比制剂R）。药物血清质量浓度以高效液相色谱法测量,药代动力学参数采用3P97和ndst21w软件处理。结果头孢泊肟酯受试制剂A、受试制剂B和参比制剂R的达峰时间（Tmax）分别为（2.81±0.51）h,（2.85±0.54）h,（2.92±0.52）h,峰浓度（Cmax）分别为（3.44±0.93）μg/mL,（3.32±0.74）μg/mL,（3.47±0.80）μg/mL,0～12h药时曲线下面积（AUC0-12h）分别为（20.02±5.61）μg·h/mL,（19.28±4.23）μg·h/mL,（19.59±5.18）μg·h/mL。受试制剂A和受试制剂B对参比制剂R的相对生物利用度分别为103.16%和100.65%。结论 3种头孢泊肟酯制剂在人体内具有生物等效性。     

头孢泊肟酯片的人体相对生物利用度研究

目的 :比较国产与进口头孢泊肟酯片在正常人体内的药动学与相对生物利用度。方法 :2 4名男性健康志愿者随机交叉单次口服国产或进口头孢泊肟酯片 2 0 0mg后 ,采用反相高效液相色谱法测定血药浓度 ,用 3P97软件包计算两者的药动学参数与相对生物利用度。结果 :国产片和进口片口服吸收的药 时曲线符合一室模型。Tmax分别为 (2 .5±s0 .6 )h和 (2 .3± 0 .5 )h ,Cmax为 (3.5± 0 .6 )mg·L- 1和 (3.6± 0 .5 )mg·L- 1,AUC0 t分别为 (18± 3)mg·L- 1和 (18.0± 2 .8)mg·L- 1,AUC0 ∞ 分别为(19± 3)mg·L- 1和 (19± 3)mg·L- 1,T12 Ke分别为(2 .0± 0 .3)h和 (2 .2± 0 .4 )h。国产片相对于进口片的相对生物利用度为 (10 2± 15 ) %。经方差分析及双单侧t检验 ,各药动学参数无显著差异 (P >0 .0 5 )。结论 :国产片与进口片生物等效。