影响过氧乙酸溶液稳定性因素分析

目的考察不同的贮存条件对不同质量浓度过氧乙酸溶液稳定性的影响。方法用间接碘量法测定过氧乙酸的含量。将浓(约200g·L-1)过氧乙酸和稀(约10g·L-1)过氧乙酸分别置于5℃,20℃,35℃恒温条件下,间隔1d,2d,3d……后测定过氧乙酸的含量。结果浓过氧乙酸溶液在5℃,20℃,35℃时的有效期分别为15d,7d,3d。稀过氧乙酸溶液极不稳定,20℃下只可保存1d。结论过氧乙酸溶液极易分解,贮存温度升高和贮存时间延长,其含量明显下降。     

1%过氧乙酸溶液在不同温度中的稳定性测定

目的 考察不同温度下贮存时间对过氧乙酸稳定性的影响.方法 用间接碘量法测定过氧乙酸的含量,观察分别置于2～5 ℃、18～22 ℃、32～34 ℃贮存温度中过氧乙酸的含量.结果 放置贮存过程中,过氧乙酸逐渐分解,随着贮存时间的增加,其含量呈下降趋势.结论 过氧乙酸在不同温度和储存条件下,其有效期也不同.     

聚乙烯吡咯烷酮对吲哚美辛的抑晶作用

吲哚美辛的玻璃化温度约为50℃。在30℃条件下，无定形的吲哚美辛经过数周即可全部转化为晶体状态；在4℃条件下这种转晶过程可延长至6个月。提高玻璃化温度或降低贮存温度可延缓药物的晶型转化。本文报道了将不同比例的蚓供美辛和聚乙烯毗咯烷酮混合制成共沉淀物，了解蚓供美辛在共沉淀物中的结晶现象。差示扫描法显示，叫跌美李聚乙烯毗咯烷酮共聚物的玻璃化温度随着聚乙烯毗咯烷酿比例的增大而升高。聚乙烯毗咯烷酮含量在50％以内时，共沉淀物玻璃化温度的变化符合Gor－don－Taylor方程：Tg1，Tg2，Tgmix分别为组分1，2和混合物的玻璃…     

不同温度下1％普鲁卡因溶液的稳定性研究

目的:考察普鲁卡因溶液在不同温度下的稳定性,探讨合理的保存条件及贮存期限。方法:用分光光度法及经典恒温法测定其相对百分含量,来推导其分解程度。结果:随着温度的升高,普鲁卡因水溶液的分解加快。结论:普鲁卡因溶液(pH=5～6)在低温条件下可减缓分解,在一般温度(25℃)下,有效贮存期限为1年半左右。     

复方无环鸟苷溶液的稳定性研究

本文采用化学动力学方法，对复方无环鸟苷溶液的稳定性进行了研究。结果表明，本品在不同温度下的贮存时间如下：５℃，２２５天；２０℃，４０天；３５℃，８天。     

那格列奈的多晶型及转化

目的：研究那格列奈的多晶型及相互转化。方法：采用了不同的溶剂、不同的温度以及研磨等晶型转化方法，晶型判定方法为X-射线粉末衍射法。结果：发现了另外一种那格列奈的新晶型，命名为X2型，并发现，H型可转变为X2型，X2型可转变为B型，H型、X2型、B型可转变为S型，H型、S型、B型可转变为无定型。结论：那格列奈的各晶型之间可以相互转化同时确立了几种晶型之间相互转化的条件。     

鬼臼毒素脂质体的稳定性研究

目的预测鬼臼毒素脂质体的稳定性。方法采用离心-分光光度法测定稳定性参数(KE)值。采用经典恒温加速试验法分别在25,30,40℃恒温条件下,在不同间隔时间用高效液相色谱法测定鬼臼毒素脂质体中药物浓度,预测鬼臼毒素脂质体在4℃下的有效期t0.9。结果在光照条件下放置10 d的KE值较0 d增加的最多,增加了12.21倍,而在4,25,30,40℃放置10 d的KE值较0 d分别增加了3.88,5.85,6.96,8.12倍;鬼臼毒素脂质体在4℃下的有效期t0.9为5 d,t0.5为60 d。结论鬼臼毒素脂质体的稳定性与温度有关,温度越高,稳定性越差,应低温保存。     

0．02％呋喃西林溶液的贮存期预测

目的预测0．02％呋喃西林溶液的贮存期。方法用分光光度法于波长376nm处测定0．02％呋喃西林溶液的含量,采用经典恒温实验法预测其在25℃时的贮存期。结果测得0．02％呋喃西林溶液25℃预测贮存期为130d,与留样观察结果相符。结论0．02％呋喃西林溶液的贮存期可定为4个月,以10～25℃、避光条件下贮存为宜。     

神经生长因子（NGF）制剂的稳定性试验

目的：研究神经生长因子（NGF）冻干制剂及其水溶液在不同条件下贮存的稳定性。方法：将纯化得到的小鼠颌下腺2.5S NGF加入赋形剂和保护剂制成冻干制剂及其水溶液。冻干制剂-20℃以下,4℃,室温和40℃贮存。水溶液在4℃和40℃贮存。经6,30,60,90,180和360d测定各样本的活性。结果：冻干制剂在20℃以下和4℃贮存360d,室温贮存90d40℃贮存30d,其活性保持稳定。水溶液在4℃贮存60d,40℃贮存6d,活性无改变。结论：NGF冻干制剂是稳定的,较高的温度和温度不利于贮存。     

不同晶型氟氯西林钠在水中溶解度的测定和关联

目的 测定不同晶型氟氯西林钠的溶解度,为进一步研究氟氯西林钠生物利用度及多晶型现象提供依据.方法 本文采用静态法测定了20～40℃范围内氟氯西林钠无定形和晶型Ⅰ-Ⅲ在纯水中的溶解度,并且采用Apelblat溶解度经验方程对实验数据进行了关联,回归了溶解度经验方程的参数.结果 获得了各晶型不同温度下溶解度的测量值和计算值,相对偏差在-2%～3%之间,关联效果令人满意.结论 在水中,氟氯西林钠各晶型的溶解度均随温度的升高而增大;在相同温度下,晶型Ⅲ和无定形具有更好的溶解性质.     

尼莫地平固体分散物的研究

尼莫地平临床上主要用于防治缺血性脑血管疾病．该药为难溶性药物，生物利用度低，本文采用了固体分散技术制备了尼莫地平两种固体分散物，其体外溶出速率１０分钟以内达８０％以上，较市售片有显著提高．两种固体分散物中，固体分散物Ⅰ为本实验室研制，固体分散物Ⅱ参照国内、外文献用ＰＶＰ为载体制备．两种固体分散物均能明显提高尼莫地平的体外溶出速率，但固体分散物Ⅱ易于老化，经相对湿度ＲＨ７５％４０℃贮藏３个月溶出速率明显下降，同样条件下，固体分散物Ⅰ则无明显变化．二种固体分散物Ｘ－射线衍射图谱表明尼莫地平以非晶体状态存在，而在ＲＨ７５％４０℃条件下放置３个月后，固体分散物ⅡＸ－射线衍射图谱出现了尼莫地平结晶峰．     

HPLC法测定尼莫地平软胶囊的含量及有关物质

目的:建立HPLC法测定尼莫地平软胶囊的有关物质及含量。方法:采用Diamonsil C18色谱柱(250 mm×4.6 mm,5μm),以甲醇-乙腈-水(35∶38∶27)为流动相,流速1.0mL.min-1,柱温为40℃,检测波长为235 nm。结果:尼莫地平和杂质A均在0.1～4.0μg.mL-1浓度范围内与其峰面积呈良好线性关系(r=1.0000),最低检出限均为0.4 ng。高、中、低3种浓度的平均回收率为99.6%,RSD为0.5%(n=9)。结论:该方法简便准确,重复性好,可用于尼莫地平软胶囊的有关物质和含量测定。     

Chemometric Evaluation of Near Infrared,Fourier Transform Infrared,and Raman Spectroscopic Models for the Prediction of Nimodipine Polymorphs

The objective of this study was to assess the performance of the chemometric model to predict the proportion of the recrystallized polymorphs of nimodipine from the cosolvent formulations. Ranging from 100% to 0% (w/w) of polymorph I, the two polymorphs mixtures were prepared and characterized spectroscopically using Fourier transformed infrared spectroscopy (FTIR), near-infrared spectroscopy (NIR), and Raman spectroscopy. Instrumental responses were treated to construct multivariate calibration model using principal component regression (PCR) and partial least square regression approaches. Treated data showed better model fitting than without treatment, which demonstrated higher correlation coefficient (R²) and lower root mean square of standard error (RMSE) and standard error (SE). Multiple scattering correction and standard normal variate exhibited higher R² and lower RMSE and SE values than second derivative. Goodness of fit for FTIR and NIR (R² ~ 0.99) data was better than Raman (R² ~ 0.95). Furthermore, the models were applied on the recrystallized polymorphs obtained by storing nimodipine-cosolvent formulations at selected stability conditions. The relative composition of the polymorphs differed with storage conditions. NIR-chemical imaging on recrystallized sample of nimodipine at 15°C qualitatively corroborated the model-based prediction of the two polymorphs. Therefore, these studies strongly suggest the importance of the potential utility of the chemometric model in predicting nimodipine polymorphs.     

Polymorphism in binary mixtures,as exemplified by nimodipine

The results of studies on nimodipine in the solid state demonstrate that the compound occurs in two polymorphic forms. Modification I melts at + 124°C and crystallizes as the racemic compound. Modification II (m.p. + 116°C) is a conglomerate. The two polymorphs have been characterized by means of differential scanning calorimetry, infrared, Raman, and ¹³C-NMR spectroscopy, X-ray powder diffractometry, X-ray structure analysis, pycnometry, and solubility measurements. The thermodynamic relationships are illustrated in a semi-schematic energy/temperature diagram, which gives information about the relative stability and physical properties of the two modifications. Modification II is the stable form between absolute zero and about + 90°C. The melting characteristics of the two polymorphs are illustrated by the phase diagram. Modification I is yellow. Modification II is almost white. The differences in colour are discussed with reference to the results of X-ray structure analyses and the UV-Vis spectra.     

高效液相色谱法同时测定血清中尼莫地平和尼群地平浓度

目的 建立一种同时测定尼莫地平、尼群地平血清浓度的高效液相色谱法.方法 以利眠宁为内标,Shim-Pack CLC-ODS Cts柱(150 mm×6 mm,5 μm)为色谱柱,甲醇一水(66:34)为流动相.流速为1.2 mL/min,柱温为40℃,乙酸乙酯为提取溶剂,检测波长为237 nm,进样量为20μL.结果 尼莫地平和尼群地平质量浓度在10～300 ng/mL范围内与样品和内标峰面积比值线性关系良好,最低检测质量浓度均为1 ng/mL(S/N>3),提取回收率大于62.2%,符合生物样品分析要求.结论 该方法快速、灵敏、准确,适用于临床血药浓度检测.     

Focused beam reflectance measurement to monitor nimodipine precipitation process

Crystallization of nimodipine in liquid-filled soft gelatin capsule during storage was reported for some commercial products, resulting in product recalls due to product quality and more importantly safety concerns. In this study, a real time particle monitoring tool, focused beam reflectance measurement, was used to evaluate the precipitation conditions of nimodipine in co-solvents. Upon water addition, two particle populations were discovered, appearing at different percentage of water content. Two transitions (i.e. sudden increase in particle counts) were observed, possibility related to nucleation and crystal growth of nimodipine. Furthermore, lowering storage temperature increased the tendency of nimodipine precipitation. Most critically, it was determined that with certain excipient, the drug precipitation occurred at approximately 7% (w/w) water content. Considering that all the orally administered liquid filled soft gelatin capsule shells contain residue water content as plasticizer, moisture transfer from the shell to the formulation may occur during long term storage, resulting in drug precipitation, particularly under cold temperature conditions.     

人血浆中尼莫地平的毛细管气相色谱电子捕获检测法及药代动力学

目的：建立测定人血浆中尼莫地平的毛细管气相色谱电子捕获检测法,并用本法研究尼莫地平片剂在健康人体内的药代动力学及相对生物利用度。方法：色谱柱为25 m×0.2 mm ID OV-101熔融石英毛细管柱,检测器为⁶³Ni电子捕获检测器。内标为尼群地平,血浆样品在碱性条件下用正己烷—乙酸乙酯(1∶1)提取。结果：浓度在2.0～150.0 ng.ml^-1与峰面积比呈良好线性关系,γ=0.99989。人血浆中尼莫地平的最低检出浓度为0.1 ng.ml^-1,方法重现性好,提取回收率大于80%。10名志愿者随机交叉口服单剂量100 mg二种国产尼莫地平片剂后,以本法测定其体内过程符合一室模型。二种片剂的AUC_0→∞。C_max,T_max均无显著差异。结论：尼莫地平血药浓度测定结果表明两种尼莫地平片剂生物等效,A片剂对B片剂的相对生物利用度为102.0%。     

尼莫地平速释微丸及缓释微丸的制备

目的研究尼莫地平速释微丸及缓释微丸的制备方法。方法通过溶剂蒸发-沉积法制备尼莫地平速释型及缓释型固体分散体;应用挤出-滚圆技术和离心造粒技术制备尼莫地平速释微丸及缓释微丸。结果依据处方1、2、3,采用挤出-滚圆技术制得的尼莫地平缓释微丸于1、3、5、12、18h的累积溶出百分率分别为18%、34%、49%、79%、100%;12%、18%、24%、36%、51%;42%、55%、61%、90%、100%。依据处方4、5得到速释微丸于45、90 min的累积溶出百分率分别为92%、100%;80%、89%,符合速释制剂的溶出要求。由处方6、7制备的缓释微丸于1、3、5、12、18h的累积溶出百分率分别为35%、48%、53%、77%、92%;30%、40%、47%、56%、80%。结论以国家食品药品监督管理局国家药品标准WS1-(X-171)-2003Z为依据设计的尼莫地平微丸处方较理想,制备工艺简单易行,值得广泛应用于尼莫地平微丸的工业生产。     

顶空毛细管气相色谱法测定溴化甲基纳曲酮中的残留溶剂

目的建立溴化甲基纳曲酮中有机残留溶剂的顶空毛细管气相色谱测定法。方法使用PEG-20M毛细管色谱柱(30m×0.25mm×0.25μm)进行分离;检测器为FID;进样口温度为200℃;检测器温度为250℃;柱温为35℃;顶空进样,80℃平衡40min;双蒸水为溶剂。结果有机残留溶剂能得到很好的分离,线性关系和精密度良好,平均回收率为95.1%～101.6%。结论该方法简单、准确、可靠,可用于溴化甲基纳曲酮中的残留溶剂的测定。     

Controlled poorly soluble drug release from solid self-microemulsifying formulations with high viscosity hydroxypropylmethylcellulose

The objective of this work was the development of a controlled release system based on self-microemulsifying mixture aimed for oral delivery of poorly water-soluble drugs. HPMC-based particle formulations were prepared by spray drying containing a model drug (nimodipine) of low water solubility and hydroxypropylmethylcellulose (HPMC) of high viscosity. One type of formulations contained nimodipine mixed with HPMC and the other type of formulations contained HPMC and nimodipine dissolved in a self-microemulsifying system (SMES) consisting of ethyl oleate, Cremophor RH 40 and Labrasol. Based on investigation by transmission electron microscopy (TEM), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray powder diffraction, differences were found in the particle structure between both types of formulations. In vitro release was performed and characterized by the power law. Nimodipine release from both types of formulations showed a controlled release profile and the two power law parameters, n and K, correlated to the viscosity of HPMC. The parameters were also influenced by the presence of SMES. For the controlled release solid SMES, oil droplets containing dissolved nimodipine diffused out of HPMC matrices following exposure to aqueous media. Thus, it is possible to control the in vitro release of poorly soluble drugs from solid oral dosage forms containing SMES.