美托洛尔片的离子选择电极法测定

目的:建立用聚氯乙烯(PVC)膜美托洛尔电极测定美托洛尔片含量的方法.方法:利用该电极对美托洛尔的响应,测定美托洛尔片含量.结果:电极的Nernst响应范围为1.0×10-2～3.2×10-5mol·L-1,级差为30 mV/pC,检出限为2.0 × 10-5mol·L-1.结论:聚氯乙烯膜电极法可简便、快速、准确地检测片剂中美托洛尔的含量.     

PVC膜离子选择电极测定盐酸地尔硫(艹卓)片

以盐酸地尔硫(艹卓)与四苯硼酸钠形成的缔合物为电活性物的聚氯乙烯(PVC)膜盐酸地尔硫(艹卓)选择电极,测定了盐酸地尔硫(艹卓)片的含量.电极的线性响应范围为1.0×1~(-5)~1.0×10~(-2)mol/L,级差电位为56mV/pc,检测限为3.2x10~(-6)mol/L.     

黄连素离子选择电极的研制

本工作对黄连素离子选择电极进行了研制。用这种电极测定黄连素有简便快速的特点。膜用聚氯乙烯为基体,邻苯二甲酸二丁酯为增塑剂,黄连素—四苯硼盐为电活性物质。所制成的电极对药根碱,小蘗胺及其它一些生物碱具有一定的选择性,可不经预先分离直接测定片剂中黄连素的含量。     

全固态咳必清电极的性能与应用研究

本文以金属铜为基体,以磷钨酸咳必清为电活性物,研究了全固态咳必清电极的性能。电极响应快速、选择性好,Nernst响应下限可达2×10~(-6)M,适用pH范围2.2～7。确定;活性膜层厚度、膜浓度与内阻、增塑剂种类对电极性能有显著影响。电极可用于药物制剂、尿、血等样物中咳必清的快速测定。提出了微体积中咳必清的快速分析方法。     

全固态咳必清电极的性能与应用研究

本文以金属铜为基体,以磷钨酸咳必清为电活性物,研究了全固态咳必清电极的性能。电极响应快速、选择性好,Nernst响应下限可达2×10^-6M,适用pH范围2.2～7。确定;活性膜层厚度、膜浓度与内阻、增塑剂种类对电极性能有显著影响。电极可用于药物制剂、尿、血等样物中咳必清的快速测定。提出了微体积中咳必清的快速分析方法。     

盐酸苯海拉明片的离子选择电极法测定

以苯海拉明与碘的分子缔合物为电活性物的 PVC膜苯海拉明选择电极 ,测定盐酸苯海拉明片的含量。电极的线性响应范围 0 .1～ 2× 10 - 5m ol/ L ,级差电位为 5 0 m V / p C,检测限为 1.4× 10 - 5mol/ L。该电极响应迅速 ,重现性好。     

离子选择电极法测定三黄片中盐酸小檗碱的含量

以小檗碱溴汞酸盐为电活性物制备PVC膜离子选择电极,用以测定三黄片中盐酸小檗碱的含量。电极的线性范围1.0×10~(-3)～5.0×10~(-7)mol/L,级差56mV/pC,检测下限2.3×10~(-7)mol/L,平均加样回收率100.3％,RSD0.75％。     

复方奎宁注射液中盐酸奎宁的一阶导数分光光度测定

采用一阶导数分光光度法测定复方奎宁注射液中的盐酸奎宁，取３３７ｎｍ波长处振幅绝对值作为定量信息，相关系数ｒ＝０．９９９９，回收率为９９．８０％，ＲＳＤ为０．４５％。     

Using Potentiometric Free Drug Sensors to Determine the Free Concentration of Ionizable Drugs in Colloidal Systems

The present study investigates the use of free drug sensors (FDS) to measure free ionized drug concentrations in colloidal systems, including micellar solutions, emulsions, and lipid formulations during in vitro lipolysis. Diphenhydramine hydrochloride (DPH) and loperamide hydrochloride (LOP) were selected as model drugs. Self-diffusion nuclear magnetic resonance studies were performed and confirmed the entrapment of drugs in micelles in Brij 35 and sodium taurodeoxycholate (TDC)/phosphatidylcholine (PC) micellar solutions. The FDS measurements indicated that with a constant level of drug, the percentage of free DPH and LOP decreased from 84% to 57% and from 51% to 18%, respectively, as the concentration of Brij 35 was increased from 4.7 to 22 mM; and from 99% to 46% and from 100% to 21%, respectively, as the concentration of TDC/PC was increased from 0.49/0.04 to 8.85/0.78 mM. During the in vitro lipolysis of a lipid formulation, free drug concentration decreased with lipolysis time. The percentage of free DPH was higher than for LOP in the same colloidal system because DPH is less lipophilic than LOP. The study showed that FDS can be used to monitor the free drug concentration in colloidal systems with fast response, no sample treatment and simple data analysis.     

Solid State Kinetics of Nitrosation Using Native Sources of Nitrite

While many reactive species are known to cause N-nitrosation, trace nitrite (NO₂⁻), which may be present in several excipients, is a source of nitrosating agents in pharmaceutical formulations. In this study we have found that the salt form of NO₂⁻ can influence the favored nitrosation conditions and final amount of nitrosamine being formed. Using native levels of NO₂⁻, most likely present as ammonium nitrite (NH₄NO₂), in microcrystalline cellulose, we have determined the kinetics of nitrosamine formation in solid state with dimethylamine substrate present in metformin, used as model compound. It was found that the competing degradation of NH₄NO₂ into N₂ and H₂O limited the amount of nitrosamine formation to a great extent. Empirically modelling the kinetic data predicted reaching at maximum 1.6% conversion over a hypothetical 3-year shelf-life. These results also showed that using other sources of NO₂⁻ as spiking reagents, such as NaNO₂, may lead to unrealistic worst-case situations when the main form of NO₂⁻ in the drug product (DP) under evaluation may be NH₄NO₂. As well, measuring NO₂⁻ in freshly manufactured excipients containing NO₂⁻ potentially as NH₄NO₂ may lead to biased high NO₂⁻ content, which is not representative of the actual amounts present at the time of DP manufacture.     

高效液相法测定氨苄西林的含量

本文采用高效液相法测定氨芳西林的含量,该方法出蜂在７ｍｉｎ左右,理论塔板数大于１７００,相对标准差（ＲＳＤ）小于２％。     

CLSM as Quantitative Method to Determine the Size of Drug Crystals in a Solid Dispersion

Purpose  

To test whether confocal laser scanning microscopy (CLSM) can be used as an analytical tool to determine the drug crystal size in a powder mixture or a crystalline solid dispersion.     

HPLC法测定虫草被孢菌胶囊中腺苷的含量

目的 建立虫草被孢菌胶囊中腺苷含量测定方法.方法 采用高效液相色谱法测定虫草被胞菌胶囊中腺苷的含量.采用Hypersil C18色谱柱(4.6 mm×250 mm,5μm);流动相:磷酸二氢钾溶液(0.05 mol·L-1)-甲醇(85∶15)为流动相,流速1.0 mL· min-1,检测波长为260hm.结果 腺苷在1.011～ 50.55μg·mL-1范围内线性关系良好,线性方程为:A=60901C-2347.7,r=1;平均回收率为100.49％(n=6,RSD=1.1％).结论 本法操作简便,不受杂质干扰,精密度好,结果准确可靠,可用于虫草被孢菌胶囊的质量控制.     

A Nondestructive Technique to Determine the Rate of Oxygen Permeation into Solid Dosage Forms

The current study investigated the use of electron paramagnetic resonance (EPR) spectroscopy as a nondestructive method to quantify the partial pressure of oxygen (pO₂) in tablets and hard shell capsules. Lithium phthalocyanine crystals (LiPC) were placed inside the dosage forms. The peak-to-peak linewidth of the first derivative of the LiPC EPR spectra was measured and, by calibration tables, the oxygen partial pressure, pO₂, within the dosage form was determined. The intra-dosage form pO₂ was followed as a function of time after changing the exterior gas stream composition. Results showed initial oxygen concentrations comparable to atmospheric levels in all tablets and capsules investigated. Oxygen rapidly permeated into unsealed gelatin and cellulosic hard shell capsules. Banding at the cap/body joint significantly reduced the oxygen permeation rate. Oxygen also rapidly permeated into tablet compacts, regardless of the compressional force used during tableting, while application of a polymeric film significantly decreased the rate of oxygen permeation. This EPR technique was shown to be a suitable nondestructive method to study oxygen permeation kinetics in solid dosage forms.     

高效毛细管电泳与荧光偏振免疫法测定癫患者血清卡马西平的方法学比较

（1. ［摘要］目的建立高效毛细管电泳（HPCE）法测定癫患者血清卡马西平浓度,比较HPCE法和荧光偏振免疫方法（FPIA）分析卡马西平含量的差异性。方法HPCE法采用石英毛细管柱（27 cm×75 μm）, 运行电压18 kV,温度30 ℃,紫外检测波长280 nm,以30 mmol•L 1磷酸氢二钠（pH＝8.0）含75 mmol•L 1 十二烷基硫酸钠（SDS）为缓冲液,血样经乙酸乙酯提取后氮气吹干,再用运行缓冲液溶解,压力进样10 s。FPIA分析采用标准TDx测定方法。结果HPCE方法测定卡马西平在2.188～100.000 μg•mL 1浓度范围内线性关系良好（r＝0.998 9）,日内和日间RSD均≤5%。结论HPCE方法准确、简便、快速,与FPIA检测结果差异无显著性,因其监测成本低更适用于常规血药监测。     

Insights into Nano- and Micron-Scale Phase Separation in Amorphous Solid Dispersions Using Fluorescence-Based Techniques in Combination with Solid State Nuclear Magnetic Resonance Spectroscopy

Purpose

Miscibility between the drug and the polymer in an amorphous solid dispersion (ASD) is considered to be one of the most important factors impacting the solid state stability and dissolution performance of the active pharmaceutical ingredient (API). The research described herein utilizes emerging fluorescence-based methodologies to probe (im)miscibility of itraconazole (ITZ)-hydroxypropyl methylcellulose (HPMC) ASDs.

Methods

The ASDs were prepared by solvent evaporation with varying evaporation rates and were characterized by steady-state fluorescence spectroscopy, confocal imaging, differential scanning calorimetry (DSC), and solid state nuclear magnetic resonance (ssNMR) spectroscopy.

Results

The size of the phase separated domains for the ITZ-HPMC ASDs was affected by the solvent evaporation rate. Smaller domains (<10 nm) were observed in spray-dried ASDs, whereas larger domains (>30 nm) were found in ASDs prepared using slower evaporation rates. Confocal imaging provided visual confirmation of phase separation along with chemical specificity, achieved by selectively staining drug-rich and polymer-rich phases. ssNMR confirmed the results of fluorescence-based techniques and provided information on the size of phase separated domains.

Conclusions

The fluorescence-based methodologies proved to be sensitive and rapid in detecting phase separation, even at the nanoscale, in the ITZ-HPMC ASDs. Fluorescence-based methods thus show promise for miscibility evaluation of spray-dried ASDs.

     

Rapid Insight into Heating-Induced Phase Transformations in the Solid State of the Calcium Salt of Atorvastatin Using Multivariate Data Analysis

Purpose

To investigate the heating-induced dehydration and melting behavior of the trihydrate phase of the calcium salt of atorvastatin.

Methods

Multivariate curve resolution (MCR) was used to decompose a variable-temperature synchrotron X-ray powder diffraction (VT-XRPD) data matrix into diffraction patterns and concentration profiles of pure drug phases.

Results

By means of the MCR-estimated diffraction patterns and concentration profiles, the trihydrate phase of the drug salt was found to dehydrate sequentially into two partially dehydrated hydrate structures upon heating from 25 to 110°C, with no associated breakage of the original crystal lattice. During heating from 110 to 140°C, the remaining water was lost from the solid drug salt, which instantly collapsed into a liquid crystalline phase. An isotropic melt was formed above 155°C. Thermogravimetric analysis, hot-stage polarized light microscopy, and hot-stage Raman spectroscopy combined with principal component analysis (PCA) was shown to provide consistent results.

Conclusions

This study demonstrates that MCR combined with VT-XRPD is a powerful tool for rapid interpretation of complex dehydration behavior of drug hydrates, and it is also the first report on a liquid crystalline phase of the calcium salt of atorvastatin.