丙戊酸镁联用氯硝西泮与碳酸锂治疗躁狂症的对照研究

目的探讨丙戊酸镁联用氯硝西泮治疗躁狂症的疗效、安全、合理性.方法对符合CCMD-2-R诊断标准的62例躁狂症患者,其中40例用丙戊酸镁联用氯硝西泮;22例用碳酸锂治疗.观察疗程6周.疗效评定以躁狂量表作基础,结合我国传统的四级疗效为标准;安全、合理性以不良反应TESS量表为依据,结合药物机制综合评定.结果二组临床疗效无显著性差异.治疗全过程观察组不良反应明显低于对照组.结论丙戊酸镁联用氯硝西泮治疗躁狂症,临床疗效确切,起效时间,安全性优于碳酸锂,联用的合理性符合躁狂症治疗的优秀备选方法.     

利用CPB-PVA-PV-铋显色体系测定药物中铋含量

目的利用CPB—PVA—PV-铋的显色反应测定药物中的铋。方法在弱酸条件下，络合物的最大吸收波长为545nm。结果铋离子含量在2～30μg／50mL范围内符合郎伯比耳定律，表观摩尔系数为2、3×10^5L·mol／cm。结论该方法简单、快速，测定治疗胃溃疡药物中的铋含量，其测定结果与偶氮氯膦-DBF吸光光度法的一致。     

丙戊酸镁栓剂的制备与质量控制

目的 研究丙戊酸镁栓剂制备处方和工艺并进行质量考察. 方法 通过正交实验筛选丙戊酸镁栓剂的处方工艺, 考察主药的不同含量对溶出度的影响.采用电位滴定法测定丙戊酸镁的的溶出度. 结果 最佳基质为甘油明胶基质（甘油：明胶：水＝6：2：2）,每粒含丙戊酸镁200 mg, 累积溶出度为91%.质量控制 方法 平均回收率为99.93%（RSD ＝ 1.88 %）. 结论 该制剂制备工艺简单,质量可控.     

丙戊酸治疗婴儿痉挛症40例疗效观察

目的 以氯硝安定为对照，探讨丙戊酸对婴儿痉挛症的疗效及其依从性。方法 在60例婴儿痉挛症患儿中对比观察丙戊酸与氯硝安定对惊厥发作的疗效及不良反应。结果 丙戊酸组40例，控制24例，明显好转10例，中度好转4例，无变化2例；氯硝安定组20例，控制12例，明显好转4例，中度好转2例，无变化2例。两组疗效差异无显著。两组治疗后不良反应丙戊酸组明显低于氯硝安定组（P＜0．05），其中氯硝安定组3例因服药后出现不能缓解的副反应而换用丙戊酸治疗。结果 丙戊酸与氯硝安定对婴儿痉挛症有相似的疗效，丙戊酸毒副反应较氯硝安定低，串对该药的依从性明显低于氯硝安定。     

丙戊酸钠添加硝西泮治疗儿童癫痫全身性发作36例

目的比较丙戊酸钠添加硝西泮和丙戊酸钠添加氯硝西泮治疗儿童癫痫全身性发作的疗效、安全性及依从性。方法选择儿童全身性发作癫痫病人59例．随机分两组分别给予丙戊酸钠添加硝西泮36例和丙戊酸钠添加氯硝西泮23例治疗,并随访观察疗效及不良反应。结果丙戊酸钠添加硝西泮治疗组与丙戊酸钠添加氯硝西泮组疗效相近,但不良反应少,性价比高。依从性好。结论丙戊酸钠添加硝西泮治疗儿童癫痫全身性发作疗效确定且价格低廉,值得在基层推广。     

三溴偶氮氯膦褪色分光光度法测定顺铂注射液的含量

目的建立催化动力学分光光度法测定常用抗肿瘤药顺铂注射液含量的方法。方法在硫酸介质中,进行顺铂催化溴酸钾氧化三溴偶氮氯膦的褪色反应,褪色程度与顺铂含量呈线性关系,利用催化动力学分光光度法进行测定。结果顺铂-三溴偶氮氯膦-溴酸钾反应液的最大吸收峰在530 nm,3-24 ng.mL-1内线性关系良好（r=0.999 1）,平均回收率为99.3%,RSD为1.24%（n=3）。结论本方法灵敏度高、操作简便快速,可用于顺铂注射剂的含量测定。     

荧光偏振免疫法检测不同储存条件血清丙戊酸浓度

目的 考察不同储存条件对血清丙戊酸浓度的影响, 并对丙戊酸稳定性进行考察. 方法 利用荧光偏正免疫分析仪（TDXFLX）对不同储存条件下的丙戊酸患者血清进行测定. 结果 血清在－30, －80 ℃储存24, 48 h, 与0 h（室温）比较, 血清丙戊酸浓度变化较大, 样品在－80 ℃冰箱储存较－30 ℃冰箱储存血药浓度稳定. 患者丙戊酸血样在－80 ℃冰箱储存达120 h后, 与0 h比较变异系数<15%. 结论 该 方法 操作简便, 快速, 结果 可靠, 可为临床患者血样监测提供便利.     

丙戊酸镁联合富马酸奎硫平治疗快速循环型双相情感障碍的效果观察

目的 探讨丙戊酸镁缓释片联合富马酸奎硫平治疗快速循环型双相情感障碍的效果.方法 42例随机分为治疗组和对照组,每组21例.治疗组给予丙戊酸镁缓释片联合富马酸奎硫平治疗,对照组给予单用丙戊酸镁缓释片治疗,均治疗2个月后评定临床疗效,随访2年,观察复发情况.结果 治疗组总有效率高于对照组,治疗后治疗组EI评分显著高于对照组,治疗组复发率明显低于对照组,差异有统计学意义(P<0.05,P<0.01).结论 丙戊酸镁缓释片联合富马酸奎硫平治疗快速循环型双相情感障碍效果明显,复发率低.     

丙戊酸镁缓释片与碳酸锂治疗躁狂发作的对照研究

目的比较丙戊酸镁缓释片与碳酸锂对躁狂发作的疗效。方法80例躁狂发作病人随机分为丙戊酸镁缓释片治疗组和碳酸锂治疗组,以Bech-Rafaelsen躁狂量表（BRMS）、临床疗效总评量表（CGI）评定疗效,用副反应量表（TESS）评定药物不良反应,于治疗前、治疗后2周、4周后各评1次。结果治疗后两组BRMS评分均下降,治疗2周后丙戊酸镁缓释片组疗效于碳酸锂组相似,治疗4周后丙戊酸镁缓释片组有效率为75%,碳酸锂组为80%,两组疗效无统计学差异。但丙戊酸镁缓释片组不良反应轻。结论丙戊酸镁缓释片治疗躁狂发作有效,安全性优于碳酸锂。     

容量法测定丙戊酸镁缓释片含量的不确定度分析

目的：容量法测定丙戊酸镁缓释片含量,并对其进行不确定度评定。方法：用EDTA滴定液络合供试品溶液中的镁离子,通过金属指示剂的变色原理确定滴定终点,获得消耗ETDA滴定液的体积（滴定时颜色从紫色变为蓝色,即为滴定终点）,以滴定度求算丙戊酸镁含量;再建立计算含量的数学模型,找出影响不确定度的因素,并对各个分量进行评估。结果：丙戊酸镁缓释片标示百分含量为99.1%,扩展不确定度为1.0%（k=2）。结论：EDTA容量法测定丙戊酸镁缓释片含量的绝对误差小于0.5%,相对误差保持在0.5%以下,该不确定度评定结果准确、可靠,为该类药品检验提供技术指导;通过分析影响不确定度的因素,找出影响检测结果的主要原因,提高检测结果的可信度。     

Properties of enteric coated sodium valproate pellets

The influence of subcoat application and micro-environmental pH on the dissolution properties of enteric coated sodium valproate pellets was investigated. The pellets were prepared by solution-layering or wet-mass extrusion-spheronization methods. In order to pass the USP enteric test, the solution-layered and wet-mass extruded pellets required 35 and 25% weight gain of Eudragit L 30D-55, respectively. The application of a subcoat of either Methocel-E5 (HPMC) or Opadry AMB to the pellets resulted in a delay in sodium valproate release in 0.1N HCl. Further delay in drug release was observed when citric acid was present in a HPMC subcoat or when added to the core pellet formulation. The amount of drug released from coated pellets was a function of the level of citric acid in the pellet core or subcoat and subsequent micro-environmental pH of the pellets. Citric acid exerted a plasticizing effect on the enteric polymer film and improved film formation and polymer coalescence. When greater than 10% (w/w) citric acid was present in the pellets, a decrease in drug content was observed due to the conversion of sodium valproate to the volatile compound, valproic acid. Pellets containing less than 10% (w/w) citric acid maintained potency during processing.     

紫外-可见分光光度法测定右旋糖酐铁制剂中铁的含量

目的:建立以紫外-可见分光光度法测定右旋糖酐铁制剂中铁含量的方法。方法:在酸性条件下,加热右旋糖酐铁溶液使Fe~(3+)游离后,用盐酸羟胺还原成Fe~(2+),再与邻二氮菲形成红色络合物,以紫外-可见分光光度法在510 nm波长处测定其含量。结果:Fe~(2+)检测浓度的线性范围为0.5～4.0μg·mL~(-1)(r=0.999 9);右旋糖酐铁片及其注射液的平均回收率分别为99.8% (RSD=0.52%)、99.7%(RSD=0.44%)。结论:本方法操作简便、结果准确,可用于该类制剂的含量测定。     

羟基红花黄色素A-磷脂复合物及其微丸的制备研究

目的：确定羟基红花黄色素A-磷脂复合物及其微丸的制备工艺。方法：以羟基红花黄色素A与磷脂的复合率为指标,通过正交试验对羟基红花黄色素A-磷脂复合物的制备条件进行优化。应用挤出-滚圆技术制备羟基红花黄色素A-磷脂复合物微丸,以综合指标为微丸质量评价指标,通过正交试验对制备条件进行优化。使用转篮法考察微丸中羟基红花黄色素A在不同介质中的溶出度。结果：羟基红花黄色素A-磷脂复合物的最佳制备条件为：羟基红花黄色素A与磷脂用量比1∶3,反应时间2小时,反应温度40℃;微丸的最佳制备条件为：黏合剂浓度3%,滚圆时间10分钟,滚圆转速20 Hz。微丸内羟基红花黄色素A在pH分别为6.8和7.4的磷酸盐缓冲溶液及去离子水中均可很好地溶出3,0分钟内溶出度达90%以上。结论：该处方工艺制备的羟基红花黄色素A-磷脂复合物微丸质量符合应用要求。     

当归补血微丸的制备及其质量控制

目的制备当归补血微丸并建立其质量控制方法。方法以挤出滚圆法制备当归补血微丸,考察微丸的粉体学性质和溶散时限,并采用高效液相色谱法测定微丸中阿魏酸的含量。结果所制微丸圆整度、流动性好,溶散时限合格。阿魏酸进样量在0.03438μg~1.146μg范围内线性关系良好(r=0.9998),平均回收率为97.0%(RSD=0.664%)。结论该制剂制备方法可行;所建立的含量测定方法准确、灵敏、稳定性好,可用于该制剂的质量控制。     

Enhanced dissolution,stability and physicochemical characterization of ATRA/2-hydroxypropyl-β-cyclodextrin inclusion complex pellets prepared by fluid-bed coating technique

The aim of this work was to prepare stable all-trans-retinoic acid (ATRA)/2-hydroxypropyl-β-cyclodextrin (HPCD) inclusion complex pellets with industrial feasible technology, the fluid-bed coating technique, using PVP K30 simultaneously as binder and reprecipitation retarder. The coating process was fluent with high coating efficiency. In vitro dissolution of the inclusion complex pellets in 5% w/v Cremopher EL solution was dramatically enhanced with no reprecipitation observed, and significantly improved stability against humidity (92.5% and 75% RH) and illumination (4500 lx ± 500 lx) was achieved by HPCD inclusion. Differential scanning calorimetry and powder X-ray diffractometry confirmed the absence of crystallinity of ATRA. Fourier transform-infrared spectrometry revealed interaction between ATRA and HPCD adding evidence on inclusion of ATRA moieties into HPCD cavities. Solid-state ¹³C NMR spectrometry indicated possible inclusion of ATRA through the polyene chain, which was the main reason for the enhanced photostability. It is concluded that the fluid-bed coating technique has the potential use in the industrial preparation of ATRA/HPCD inclusion complex pellets.     

Preparation, characterization, and controlled release from coprecipitates of fluorescein and magnesium hydroxide

Magnesium hydroxide was precipitated as a lyophobic sol in the presence of various concentrations of fluorescein sodium (3'6'-dihydroxyspiro[isobenzofuran-1(3H),9'-[9H]xanthen++ +]-3-one, disodium salt) ranging in molar equivalents between 0.1 and 2 times that of the hydroxide. Coprecipitates were washed and dried, and release of the dye and magnesium was determined (pH 7.4, 37 degrees C) from rotating disks. Release rates varied depending upon fluorescein content. The rate of dye release was retarded by less than or equal to 10(4) times that of fluorescein sodium alone, implying the existence of some form of solid association between the components of the coprecipitates. The presence of the dye in certain concentrations reduced magnesium hydroxide dissolution rates by a factor of three. Fluorescein dissolution rates, when expressed as percent release, passed through a minimum (coincident with the dye-induced reduction in Mg(OH)2 dissolution). Adsorption experiments revealed evidence for multiaffinity binding of fluorescein at the surface of freshly precipitated Mg(OH)2. Magnesium, fluorescein, and water contents of the coprecipitates were characterized by atomic absorption and UV spectroscopy and by thermogravimetric analysis. Fluorescein content increased in direct proportion to its initial concentration in solution. Controlled, but variable release of this easily assayed dye is possible by employing precipitates with different fluorescein contents.     

Stability of sodium valproate tablets repackaged into dose administration aids

Objectives Since sodium valproate, a commonly used antiepileptic drug, has been reported to be unstable in the presence of moisture, our objective was to investigate the effect of repackaging into dose administration aids. Methods Sodium valproate 100 mg immediate‐release tablets were repackaged and stored for 56 days at accelerated conditions (40°C/75% relative humidity), room temperature (25°C) and under refrigeration (2–8°C). Samples were analysed at 3, 7, 10, 14, 21, 35, 49 and 56 days to determine chemical stability using high‐performance liquid chromatography, while physical testing included assessment of weight changes and dissolution behaviour. Key findings The results revealed that the sodium valproate content in the tablets remained within the acceptable range of 90–110% under all storage conditions for 56 days. Physical stability, however, was not maintained, with a total weight gain of 12.36% under accelerated conditions over the 56 days. Samples stored under all conditions showed variable dissolution compared to the controls, with the amount of sodium valproate in solution following 45 min of dissolution testing below 75% for half of all the intervals determined. Conclusions Repackaging sodium valproate tablets into dose administration aids results in unacceptable weight variation and changes in the dissolution profiles.     

Formulation and characterization of extruded and spheronized pellets using pectin and crosslinking agents

The aim of this study was to prepare pellets of gliclazide by extrusion spheronization process by use of two methods in situ cross linking method and interracial complexation method and to study the effect of different cross linking agents on the formed pellets. Extrusion/spheronization being an established technique for producing spherical pellets so this technique was used to prepare pellets. The gliclazide pellets prepared by extrusion-spheronization techniques and then the formed pellets were coated with pectin solution by interfacial complexation method. The effect of cross-linkers calcium chloride and aluminium chloride concentration, by in situ cross linking on properties of gliclazide pellets like swelling and drug release were studied. The formed pellets were subjected to swelling, analysis of morphology, in dissolution and vivo studies. Most of the pellets were of acceptable shape. From the results calcium chloride when coated with pectin, retarded drug release. As the concentration of calcium chloride increased, it led to slow release of the drug. This may be due to the water solubility of calcium salt, which induced cross linking with pectin. Thus pellets with calcium chloride cross linked with pectin were beneficial, because it retarded the release of the drug. Though the release from interfacial coated pellets was retarded, it was less as compared to the in situ formed pellets. The in vivo studies on alloxan-induced diabetic rats indicated the significant hypoglycemic effect that was observed 24 h after oral administration of optimized pellets. Thus, the developed and optimized pellets were suitable for prolonged systemic absorption of gliclazide to maintain lower blood glucose level and improved patient compliance. The results suggested that the in situ cross linking pellets were able to retard the release of gliclazide greater than the interfacial complexation method. Therefore, this approach has been effectively achieved.     

头孢呋辛酯掩味微丸的制备

目的:制备头孢呋辛酯掩味微丸。方法:采用离心造粒粉末层积法制备头孢呋辛酯含药素丸,在此基础上进行水分散体掩味包衣,并测定制剂体外溶出度。结果:所得含药微丸40～50目,收率为89.5%,载药量为6.29%,45min时的溶出度达到80%。结论:采用水分散体包衣成功地制备了头孢呋辛酯掩味微丸。