Zero-order release formulations using a novel cellulose ester

New carboxymethylcellulose esters were developed with useful properties for oral dosage forms in drug delivery. Normally, commercial cellulose esters are used as the major excipients in oral dosage forms as a coating or a membrane. In applications involving compression tablets, cellulose esters are usually mixed with other more hydrophilic matrix components to facilitate dissolution of the active. In the present study, novel cellulose esters were single component matrix resins. Pharmaceutical actives were cryogenically ground as a physical blend or an amorphous blend with the polymer. Subsequently, tablets were made by direct compression using a single tablet press, or capsules were made by filling them with the ground material. Dissolution tests were completed on the solid dosage forms at pH 1.2, 4.5, 6.8 or 7.4 in a United States Pharmacopeia (USP) II device to determine the release profiles for up to 24 h. Carboxymethylcellulose esters provide an excellent matrix for controlling both the rate of release and the pH at which pharmaceutical actives release into the aqueous environment. When used in suitable quantities, dictated by the active of interest, carboxymethylcellulose acetate butyrate provided zero-order release over sustained time up to 24 h.     

Qualitative and quantitative analysis of the major constituents in Jin‐Mu‐Gan‐Mao tablet by high‐performance liquid chromatography with diode‐array detection and quadrupole time‐of‐flight tandem mass spectrometry

Jin‐Mu‐Gan‐Mao tablet is a well‐known traditional Chinese medicinal preparation, which has been used to treat the common cold in China. In this study, a systematic method was established for the qualitative and quantitative analysis of the major constituents in Jin‐Mu‐Gan‐Mao tablet. First, a method of high‐performance liquid chromatography with diode‐array detection and quadrupole time‐of‐flight mass spectrometry was developed for identification of the multi‐constituents. Thirty‐one compounds including ten phenolic acids, 18 flavonoids, and three iridoid glycosides were clearly identified by comparison with the reference standards, and 11 compounds were deduced by comparison with the literature data. Second, a new quantitative analysis method of Jin‐Mu‐Gan‐Mao tablet was established by high‐performance liquid chromatography with diode‐array detection. Twelve compounds, either with high contents or strong bioactivities, were chosen as marker components. This analytical method was validated through intra‐ and interday precision, repeatability, and stability, with respective relative standard deviations less than 1.74, 2.54, 2.44, and 2.48%. The limits of detection and quantification were less than 0.327 and 0.881 μg/mL, respectively. The overall recoveries ranged from 97.04–102.76% (relative standard deviation ≤ 2.91%). Then this validated method was applied to determine ten batches of Jin‐Mu‐Gan‐Mao tablet. The results indicated that these new approaches can be applicable for the qualitative and quantitative analysis of Jin‐Mu‐Gan‐Mao tablet.     

测量复方药物溶出度的全自动药物溶出度测定仪

自行设计组装了一套可以同时测定复方药剂的全自动药物溶出度测定仪。该仪器由光学检测系统（由光源、流动型吸收池，小型光谱仪组成）、自动进样系统、控制与数据处理系统和机械搅拌系统4部分组成。光学系统的检测器是线阵电荷耦合器件（CCD），故可进行同时全光谱采集。数据处理部分采用了自行设计的基于径向基函数的人工神经网络进行浓度预测。用本装置对市售复方药剂鲁南贝特进行的溶出度测量表明，测量的精密度高，准确度较高，分析速度快，样品无需前处理。     

通塞脉片、脉通胶囊中钾钠铬锰镍的分析研究

采用火焰原子吸收分光光度法测定了通塞脉片、脉通胶囊中K、Na、Mn、Cr、Ni的含量。结果显示,药物中钾、钠、铬、锰、镍含量具有显著性差异（P＜0．05）;镍的含量没有显著性差异（P＞0．05）。     

迭代目标因子分析-紫外分光光度法测定克感敏片三组分

本文应用迭代目标因子分析－紫外分光光度法不经分离同时测定克感敏 片中非那西丁、氨基比林、咖啡因三组分含量,其回收率和相对标准偏差分别为100．4％,0．83％,99．2％,0．77％,99．4％,0．69％。     

Development of a green effervescence-assisted dispersive liquid–liquid microextraction method using a home-made tablet disperser for trace analysis of Cd(II) and Pb(II)

An analytical approach for the determination of trace amounts of Cd(II) and Pb(II) has been developed using a home-made tablet-based effervescence-assisted dispersive liquid–liquid microextraction (DLLME) method which was performed in a narrow-bore tube, followed by flame atomic absorption spectrometry. In this method, a mixture of tartaric acid, sodium bicarbonate and NaCl was used to make the disperser tablet. Then, microlitre level of an extraction solvent was added in the tablet, and then, it was released into a narrow-bore tube containing sample solution and a complexing agent. An acid–base reaction immediately occurred between tartaric acid and sodium bicarbonate, and the produced CO₂ led to the dispersion of the extraction solvent into the solution as tiny droplets and subsequent extraction of the analytes. The method made possible the determination of Cd(II) and Pb(II) in the ranges of 0.1–10 and 1.0–20 µg L^?1, respectively. The limits of detection were obtained 0.43 and 0.05 µg L^?1 for Pb(II) and Cd(II), respectively. The limits of quantifications were 0.80 and 0.09 µg L^?1 for Pb(II) and Cd(II), respectively. Repeatability of the method, which is expressed as relative standard deviation, was obtained 3.1% (n = 6, C = 2 µg L^?1) and 1.3% (n = 6, C = 0.2 µg L^?1) for Pb(II) and Cd(II), respectively. The accuracy of the developed method was verified by analysing a certified reference material, namely SPS-WW2 Batch 108. Relative recoveries (84–107%, obtained at three fortification levels) confirmed the usefulness of the method for analysis of the analytes in the environmental water samples and fruit juices. The method was shown to be fast, reliable and environmentally friendly with low organic solvent consumption.     

Development of a sustained-release matrix tablet formulation of DHEA as ternary complex with α-cyclodextrin and glycine

Sustained-release matrix-tablets of dehydroepiandrosterone (DHEA) as ternary complex with α-cyclodextrin and glycine (c-DHEA) were prepared by direct compression with suitable excipients. The influence of the swelling properties of hydroxypropylmethylcellulose (HPMC) and the disintegrating power of Explotab^® used in combination, as well as the effect of the presence, type and amount of suitable channelling agents (Emcocel^® and spray-dried lactose, alone or in combination) on drug release behaviour from matrix-tablets has been evaluated. The best performances in terms of drug release was obtained from formulations containing a 75:25 w/w spray-dried lactose:Emcocel^® combination in the presence of HPMC as matrix-forming polymer, leading to a more than 65% DHEA released at the end of the test, a value which was, respectively, 1.9 and 2.7 times higher than those achieved with the corresponding formulations containing spray-dried lactose or Emcocel^® alone. The drug release profile from the most effective matrix-tablet formulation of c-DHEA allowed achievement of a more than 6-fold increase in the drug amount released within 24 h in comparison with the same formulation containing the simple physical mixtures of DHEA, α-cyclodextrin and glycine. Therefore the advantage of using DHEA as ternary complex, prepared by mechano-chemical treatment, was clearly demonstrated, thus allowing the development of an effective sustained-release formulation of the drug.     

A solid-phase enzyme-linked assay for vitamin B12

A new solid-phase enzyme-linked competitive binding assay for vitamin B₁₂ (cyanocobalamin) is described. The assay is based on the competition between analyte B₁₂ molecules and a glucose-6-phosphate dehydrogenase-vitamin B₁₂ conjugate for a limited number of R-protein binding sites immobilized on sepharose particles. After appropriate incubation and washing steps, the enzyme activity bound to the solid-phase is inversely related to the concentration of B₁₂ in the sample. Under optimized conditions, the method can detect B₁₂ in the range of 3×10^–10–1×10^–8 M (using 100l sample) with high selectivity over other biological molecules.     

Fast Melt Cocoa Butter Tablet: Effect of Waxes,Starch, and PEG 6000 on Physical Properties of the Preparation

A fast melt tablet (FMT) is well regarded as an alternative delivery system that might help resolve a patient’s non-compliance issue. The main objective of this study was to develop a cocoa butter-based FMT. Additives, namely 5–15% of PEG 6000, beeswax, paraffin wax, and corn starch, were incorporated into the cocoa butter-based FMT to study the effects of these additives with the physical characteristic of a cocoa butter FMT. An optimum-based formulation was chosen according to the desired hardness and disintegration time and the taste masking property achieved with the model drug—dapoxetine. The analysis demonstrated that incorporating beeswax (15%) and paraffin wax (15%) could prolong the disintegration time by at least two-fold. On the contrary, the presence of corn starch was found to cause an increase in the hardness and reduction of the disintegration time. The disintegration mechanism might be presumed due to the synergistic effect of starch swelling and cocoa butter melting. The hardness value and in vitro disintegration time of the optimum formulation were recorded at 2.93 ± 0.22 kg and 151.67 ± 6.98 s. In terms of dissolution, 80% of dapoxetine was released within 30 min and the dissolution profile was comparable to the innovator product. The formulation was palatable and stable for at least 1 year. The exposure of the FMT formulation at 30 °C for 12 months was reported to be stable. Along with the sound palatability profile and high drug load capacity, the current formulation possesses the desired characteristics to be scaled up and marketed.     

电感耦合等离子质谱法测定古汉养生精中铅砷镉铬镍

研究了微波消解样品,电感耦合等离子质谱(ICP-MS)法同时测定样品中铅、砷、镉、铬、镍等有害元素。对影响其测量的各种因素包括射频功率、载气流量、采样深度等进行了研究。方法的检出限为0.001~0.008μg.L-1,回收率为84.6%~115.0%,RSD为1.84%~4.30%。