Oral Sustained-release Cisplatin Preparation for Rats and Mice

A new oral sustained-release solid-dispersion preparation of cisplatin (cis-diamminedichloroplatinum(II); cisplatin) has been developed for administration to small experimental animals such as mice. This preparation was obtained by formulating cisplatin with the water-insoluble polymer ethylcellulose and with stearic acid in different ratios. In-vitro dissolution studies showed that cisplatin release characteristics were zero-order for the formulation cisplatin–ethylcellulose–stearic acid (1:10:5) and levels equilibrated 7 h after the start of the experiment. The availability of cisplatin from this preparation was evaluated both in rats and mice. The cisplatin preparation (20 mg kg^?1) was administered orally to rats and the resulting curve of serum cisplatin levels against time was compared with that obtained after intravenous infusion (20 mg kg^?1) to rats. By comparing the areas under serum concentration-time curves (AUCs), the bioavailability of cisplatin was estimated to be 31%. The mean residence time (MRT) of cisplatin solid dispersion was 6.13 ± 0.43 h, whereas the MRT of cisplatin administered by intravenous infusion was 3.89 ± 0.05 h. Serum cisplatin levels were maintained above 0.3 mg mL^?1 (believed from our clinical studies to be the minimum effective concentration) for 24 h. The curve of serum cisplatin level against time suggested that cisplatin was released from the solid dispersion preparation in a sustained-release fashion. Similar levels were also maintained in mice for 24 h. The MRT of the cisplatin preparation was 10–16 h in mice, which is longer than that obtained after oral administration of the physical mixture. The serum free-cisplatin concentration was determined to be 0.10 mg mL^?1 in mice serum in which the total cisplatin concentration was 0.30 mg mL^?1. The free fraction of cisplatin in mice serum was the same as that in human patient serum. Pathological examination showed that this new sustained-release oral cisplatin preparation did not have any side effects on the gastrointestinal tract. These results suggest usefulness of this new solid-dispersion preparation for oral cisplatin therapy in lung cancer patients.     

布洛芬缓释胶囊生物利用度研究

10名健康志愿者随机交叉口服600mg布洛芬缓释胶囊和芬必得进行药代动力学和相对生物利用度研究。采用高效液相色谱法，测定血清中布洛芬浓度，经3p87药动学计算程序处理，得布洛芬缓释胶囊和芬必得的：AUC分别为147．75±28．78：mg／（L·h）和154．16±26．76mg／（L·h），Tmax分别为4．22±0．73h和4．10±0．83h；Cmax分别为15．97±2．84mg／L和16．76±2．92mg／L，经配对ｔ－检验，两者的AUC、Tmax、Cmax均无显著性差异（P＞0．05）。采用梯形法计算的布洛芬和芬必得的AUC。－t分别为153．53±26．11mg／（L·h）和157．88±23．06mg／（L·h），方差分析和双单侧检验结果表明两者具有生物等效性。布洛芬缓释胶囊相对生物利用度为96．07％。     

复方土牛膝缓释口炎膜治疗口腔溃疡临床疗效

目的：观察复方土牛膝缓释口炎膜在治疗口腔溃疡中的临床疗效及不良反应。方法：将临床确诊为口腔溃疡的患者随机分为两组,进行疗效对照比较。治疗组用复方土牛膝缓释口炎膜,对照组用甲硝唑醋酸洗必泰含漱液。每天记录患者溃疡面直径及疼痛感2项指标。结果：治疗组在病灶各项指标改善程度上均优于对照组（P〈0．05）,而无不良反应。结论：复方土牛膝缓释口炎膜是一种疗效高及安全的治疗口腔溃疡药用膜剂。     

吲哚美辛缓释胶囊释放度检查的一点改进建议

吲哚美辛缓释胶囊具有抗炎、解热及镇痛作用。适用于类风湿关节炎、强直性脊柱炎、骨关节炎及痛风急性发作期,缓解症状。吲哚美辛缓释胶囊质量标准收载于国家药品监督管理局国家药品标准WS1-（X-039-2）-2001Z,检查项中的释放度,采用溶出度测定法第二法（桨法）（《中国药典》2005年版二部（附录XD））,转速为150r·min^-1。     

HPMC配制萘普生骨架型缓释颗粒胶囊的试验

目的:研究萘普生骨架型缓释颗粒胶囊的制备,减少给药次数,降低不良反应。方法采用硬脂酸包裹和羟丙甲基纤维素(HPMC)水凝胶缓释技术及UV测定法,研究了萘普生骨架型缓释颗粒胶囊并进行初步稳定性试验。结果萘普生检测浓度在10．0-50．0μg?ml-1范围内,紫外吸收值(A)与浓度(C)有良好线性关系,r=0．9987;本品缓释效果明显,12h内药物释放曲线符合Higuchi方程,属于扩散释药机制。结论本缓释胶囊处方合理工艺简单,有理想的缓释效果。     

右旋酮洛芬缓释胶囊的制备及体外释药研究

目的:研究右旋酮洛芬缓释胶囊制备的处方条件。方法:采用喷雾干燥法制备右旋酮洛芬缓释细粒,填充入胶囊制成缓释胶囊,测定缓释胶囊(或细粒)的体外释放度,并考察制备处方条件对药物释放度的影响。结果:喷雾干燥法制备右旋酮洛芬缓释细粒,填充入胶囊即为缓释胶囊;在最优处方条件下缓释胶囊1h内体外累计释药量不超过30%,24h不低于90%。结论:该处方条件的右旋酮洛芬缓释胶囊的生产工艺简单可行,最终所得的缓释胶囊具有较好的缓释特征。     

含药树脂表面修饰法制备加兰他敏口服缓释混悬液

采用离子交换吸附技术,用丙烯酸树脂RS100修饰加兰他敏(1)树脂表面,制成1的缓释混悬液。1树脂经表面修饰后,体外释药速率明显减慢。1缓释混悬液和溶液剂在大鼠体内的cmax分别为209.05和333.16ng/ml;tmax4.5和1.4h;t1/212.55和7.05h;AUC0→24h2555.67和2007.78ng·h·ml-1;绝对生物利用度(fabs)55.80%和43.84%;1缓释混悬液相对于溶液剂的生物利用度(frel)为127.29%。     

他克莫司口服自微乳骨架缓释微丸的制备及其释药机制研究

目的 制备他克莫司自微乳骨架缓释微丸,并探讨其释药机制。方法 采用星点设计-效应面法筛选他克莫司自微乳最优处方,在此基础上,采用挤出滚圆技术,以微晶纤维素(microcrystalline cellulose,MCC)为吸附剂和填充剂、乙基纤维素(ethyl cellulose,EC)与硬脂酸(stearic acid,SA)为骨架材料,以5%羟丙基甲基纤维素(hypromellose,HPMC)溶液为黏合剂,制备他克莫司自微乳骨架缓释微丸,并考察其体外溶出情况。结果 他克莫司自微乳最优处方为Crodamol EO∶Solutol HS15∶Transcutol P=15%∶52.5%∶32.5%。骨架缓释微丸最优处方为MCC用量为45%,EC∶SA用量比为3∶2,5%HPMC溶液用量为12 mL。制得的他克莫司自微乳骨架缓释微丸符合市售他克莫司缓释胶囊的体外释放标准,释药机制为溶蚀与扩散相结合。结论 优选的处方稳定可行,他克莫司自微乳骨架缓释微丸体外释放符合预期目的。     

口服恩丹西酮胶囊的人体相对生物利用度

用HPLC法测定9名健康志愿者分别口服恩丹西酮（ondancetron）片剂和胶囊各8mg后血浆药物浓度。两药的药动学参数分别为：AUC（0-∞）为194.3±28.0和195.7±33.8g／（L·h）Cmax为25.1±4.9和25．8±44pg／L；Tmax为1．5±0．5和1．4±0．5h。结果说明两制剂具有生物等效性。     

1例头孢克洛缓释胶囊诱发中毒性表皮坏死松解症的个体化治疗方案制订

目的 临床药师通过参与头孢克洛缓释胶囊引发中毒性表皮坏死松解症案例个体化治疗方案的制订,开拓临床切入点。方法 回顾临床药师依据药物诱发中毒性表皮坏死松解症的相关案例结合患者具体体征,参与1例因头孢克洛缓释胶囊引发中毒性表皮坏死松解症个体化治疗方案的制订。结果 临床药师分析该不良反应发生的原因,参照相关文献及患者实际,参与制订患者个体化治疗方案,为患者提供药学监护和用药教育,保证患者用药安全、有效。结论 临床药师依据患者诊断,参照相关案例报道并结合患者实际,制定针对个体化的治疗方案,亦可成为临床药师工作的切入点。     

倍他乐克联合参松养心胶囊治疗室性早搏的临床研究

目的探讨倍他乐克联合参松养心胶囊治疗室性早搏的临床疗效。方法选取在我院治疗的室性早搏患者94例,随机分为观察组和对照组,均给予倍他乐克进行治疗,观察组加用参松养心胶囊进行治疗,比较疗效。结果观察组总有效率为93.62%,对照组总有效率为70.21%,观察组Tpe间期和Tpe离散度明显小于对照组(P<0.05)。结论倍他乐克联合参松养心胶囊用于室性早搏治疗,可明显提高治疗效果,增加心室肌的稳定性。     

Oral Sustained-release Drug Delivery Systems using Polycarbonate Microspheres Capable of Floating on the Gastric Fluid

Abstract— Polycarbonate microspheres loaded with aspirin, griseofulvin and p-nitroaniline were prepared by a solvent evaporation technique. High drug loading (> 50%) was achieved by this process. Drug-loaded microspheres were found to float on simulated gastric fluid and intestinal fluid. Drug-release studies were carried out in these fluids at 37°C. Increasing the drug to polymer ratio in the microspheres increased both their mean particle size and the release rate of the drugs. It was concluded that sustained delivery of drugs could be effected using this matrix.     

口服单剂量地尔硫卓缓释胶囊的人体相对生物利用度研究

１２ 名男性健康志愿受试者，随机交叉一次口服法国进口的盐酸地尔硫卓缓释胶囊（ 参比品） 和国产的盐酸地尔硫卓缓释胶囊（ 试验品） 各１８０ ｍｇ，进行人体生物利用度研究，血药浓度用ＨＰＬＣ 法测定．２ 种盐酸地尔硫卓缓释胶囊，其药时曲线和药代动力学特征十分相似．参比品和试验品从胃肠吸收均有较短的滞后时间．其Ｃｍａｘ 分别为（６８－８５ ±１９－００）ｎｇ／ｍＬ 和（６９－０１ ±２２－４５）ｎｇ／ｍＬ，Ｔｍａｘ 分别为（４－５８ ±１－３７）ｈ 和（４－６９ ±２－１０）ｈ ，ＡＵＣ（０ ～３６） 分别为（１５４１－６ ±５３５－９）ｎｇ／ｍＬ·ｈ 和（１ ５６２ ±６４９－２）ｎｇ／ｍＬ·ｈ ，试验品盐酸地尔硫卓缓释胶囊的相对生物利用度（９８－５９ ±１６－９８） ％ ，试验品与参比品的ＡＵＣ（０ ～３６） ，经方差分析，２ 者的吸收程度具有生物等效性．     

头孢克洛胶囊及分散片在健康人体内的生物等效性研究

目的评价头孢克洛胶囊及分散片在健康人体内相对生物利用度及生物等效性。方法受试者采用3处理、3周期、随机、自身交叉对照方法口服受试制剂头孢克洛胶囊、头孢克洛分散片和参比制剂500mg，采用反相高效液相色谱（RP—HPLC）法测定血浆中药物浓度，药代动力学参数采用DAS软件处理。结果头孢克洛胶囊、分散片及参比制剂分散片峰浓度（Cmax）分别为（11．79±2．85）μg／mL，（13．07±3．53）μg／mL和（12．59±3．34）μg／mL；达峰时间（kmax）分别为（0．75±0．20）h，（0.62±0．17）h和（0．55±0．11）h；半衰期（tin）分别为（0．60±0．11）h，（0．56±0．08）h和（0，57±0．10）h；0→t药-时曲线下面积（AUC0→t）分别为（15．37±2．23）μg·h／mL，（16．15±3．75）μg·h／mL和（15．66±2．98）μg·h／mL；0→∞药-时曲线下面积（AUC0→∞）分别为（15．67±2．26）μg·h／mL，（16．43±3．74）μg·h／mL和（15．93±3.02）μg·h／mL；受试制剂的相对生物利用度F0→t和F0→∞分别为（100．51±19．19）％，（100．70±19．00）％和（105．96±29．16）％，（105．87±28．52）％。受试制剂与参比制剂符合生物等效标准。结论头孢克洛胶囊、头孢克洛分散片与参比制剂具有生物等效性。     

国家食品药品监督管理局国家药品标准修订件——格列吡嗪缓释胶囊

本品含格列吡嗪（C23H27N504S）应为标示量的90．0％～110．0％。[性状]本品内容物为白色球形颗粒。[鉴别]（1）在含量测定项下记录的色谱图中,供试品溶液主峰的保留时间应与对照品溶液主峰的保留时间一致。（2）取本品的内容物适量,加甲醇制成每1mL中含格列吡嗪20μg的溶液,滤过,滤液照紫外一可见分光光度法（中国药典2010年版二部附录ⅣA）测定,在226nm与274nm的波长处有最大吸收。     

吗替麦考酚酯胶囊的人体生物等效性研究

目的:评价吗替麦考酚酯胶囊在18名男性健康志愿者体内的生物等效性。方法:受试者随机、双交叉、单剂量口服试验药和对照药1 000 mg。血浆药物浓度采用HPLC法测定,色谱柱为Agilent Zorbax SB C18,流动相为乙腈:水:三乙胺磷酸溶液(35:45:30,v／v),紫外检测波长为250 nm,4-乙基苯甲酸为内标;药动学参数采用DAS软件处理获得。结果:试验药和参比药t1／2 ke分别为(17．56±19．23)和(21．55±28．36)h,Cmax分别为(45．34±16．99)和(45．11±13．78)mg·L-1,tmax分别为(0．69±0．29)和(0．74±0．33)h,AUC0-36分别为(88．92±22．32)和(90．61±21．54)mg·h·L-1。试验药相对生物利用度为99％±18％。经双单侧t检验和方差分析,两制剂符合生物等效标准。结论:试验药和参比药具有生物等效性。     

Cisplatin nephrotoxicity

Cisplatin is used widely in the treatment of a large number of carcinomas. The clinical use of cisplatin, however, can be complicated by myelotoxicity, ototoxicity and intestinal toxicity; we review briefly cisplatin nephrotoxicity. The principal route of its excretion is via the kidney, and accumulation of cisplatin in the renal cortex has been demonstrated. Three to five days following administration of cisplatin to rats, degenerative changes appear in the proximal tubule, including cytoplasmic vacuolization, tubular dilatation and pyknotic and hydropic degeneration. A decrease in renal plasma flow was observed very early on in patients receiving cisplatin at a dose of 20 mg/m2 over a period of 4 h, and an increase in urinary enzymes occurred rapidly. Hypomagnesaemia, hypocalcaemia and hypokalaemia were frequent. The mechanism of cisplatin nephrotoxicity remain unclear. Biotransformation of cisplatin could play an important role; a decrease in sulphydryl groups in the kidney may be a primary event, and reactive metabolites may be formed. The incidence of cisplatin nephrotoxicity has been observed to decrease when patients are prehydrated, and it was proposed recently that administration of a calcium blocker might reduce the nephrotoxic effects of cisplatin. The clinical recommendations are to avoid rapid cisplatin infusion rates (over 1 mg/kg per hour) and to induce hydration at least during and after cisplatin administration. New compounds with the same or better antitumour activity and less toxicity should be prepared. At present, carboplatin appears to be preferable to cisplatin because of the reduced incidence of untoward effects.     

豆腐果素缓释微丸包衣工艺的研究

分别以Surelease、Eudragit RS30D／RL30D为包衣材料，制备豆腐果素缓释微丸，筛选包衣工艺的优化参数。结果表明，用Surelease、Eudragit两种包衣材料均可得到在12h内缓慢释放的微丸，后者有近1h的时滞。     

格列吡嗪缓释片的研制

以高黏度羟丙甲纤维素和卡波姆为缓释材料,采用湿法制粒制备格列吡嗪缓释片.以含0.25%十二烷基磺酸钠的0.015 mol/L盐酸为释放介质,制品4、8、12、16和24 h的累积释放度分别为(29.9±3.2)%、(55.0±2.0)%、(78.9v2.1)%、(89.6±1.9)%和(99.3±1.5)%.体外累积释放度与体内吸收分数的相关系数r=0.983 3,表明缓释片的体内外相关性良好(P<0.001).