Synthesis and characterization of new copolymers of ethyl methacrylate grafted on tapioca starch as novel excipients for direct compression matrix tablets

In last years, the introduction of new materials for drug delivery matrix tablets has become more important. This paper evaluates the physicochemical and mechanical properties of new graft copolymers of ethyl methacrylate (EMA) on tapioca starch (TS) and hydroxypropylstarch (THS), synthesized by free radical polymerization and dried in a vacuum oven (OD) or freeze-dried (FD). Infrared and ¹³C NMR spectroscopies confirm the change of chemical structure of the copolymers and X-ray diffraction shows up the higher amorphization of copolymers respect to the carbohydrates. Particle size analysis and SEM indicate that graft copolymerization leads to an increase of particle size and a more irregular shape. Graft copolymerization implies decrease of density and moisture content values. Heckel equation shows that copolymers have less densification by particle rearrangement and fragmentation than carbohydrates. Concerning the drying methods, FD products have larger plasticity and lower elasticity than OD copolymers. Graft copolymerization produces a decrease of the applied pressure necessary to obtain tablets, ejection force and friction work. Furthermore, graft copolymers show longer disintegration time than tablets from raw starches. These qualities suggest that these copolymers could be used as excipients in matrix tablets obtained by direct compression, and with a potential use in controlled release.     

Analysis of quinocide in unprocessed primaquine diphosphate and primaquine diphosphate tablets using gas chromatography–mass spectrometry with supersonic molecular beams

Malaria is one of the most widespread and deadly diseases on the planet. Every year, about 500 million new cases are diagnosed, and the annual death toll is about 3 million. Primaquine has strong antiparasitic effects against gametocytes and can therefore prevent the spread of the parasite from treated patients to mosquitoes. It is also used in radical cures and prevents relapse. Consequently, primaquine is an often-used drug. In this study the separation of unprocessed primaquine from the contaminant quinocide based on gas chromatography–mass spectrometry with supersonic molecular beam (SMB) is presented and 7.5 mg primaquine diphosphate tablets were analyzed. We present a novel method for fast determination of quinocide which is an isomer of primaquine as the main contaminant in unprocessed primaquine and in its medical form as tablets by gas chromatography–mass spectrometry with SMB (also named supersonic GC–MS). Supersonic GC–MS provides enhanced molecular ion without any ion source related peak tailing plus extended range of compounds amenable for GC–MS analysis. In addition, major isomer mass spectral effects were revealed in the mass spectra of primaquine and quinocide which facilitated the unambiguous identification of quinocide in primaquine tablets. Fast GC–MS analysis is demonstrated with less then 2 min elution time of the drug and its main contaminants.     

Thermal desorption counter‐flow introduction atmospheric pressure chemical ionization for direct mass spectrometry of ecstasy tablets

A novel approach to the analysis of ecstasy tablets by direct mass spectrometry coupled with thermal desorption (TD) and counter‐flow introduction atmospheric pressure chemical ionization (CFI‐APCI) is described. Analytes were thermally desorbed with a metal block heater and introduced to a CFI‐APCI source with ambient air by a diaphragm pump. Water in the air was sufficient to act as the reactive reagent responsible for the generation of ions in the positive corona discharge. TD‐CFI‐APCI required neither a nebulizing gas nor solvent flow and the accompanying laborious optimizations. Ions generated were sent in the direction opposite to the air flow by an electric field and introduced into an ion trap mass spectrometer. The major ions corresponding to the protonated molecules ([M + H]⁺) were observed with several fragment ions in full scan mass spectrometry (MS) mode. Collision‐induced dissociation of protonated molecules gave characteristic product‐ion mass spectra and provided identification of the analytes within 5 s. The method required neither sample pretreatment nor a chromatographic separation step. The effectiveness of the combination of TD and CFI‐APCI was demonstrated by application to the direct mass spectrometric analysis of ecstasy tablets and legal pharmaceutical products. Copyright © 2009 John Wiley & Sons, Ltd.     

统计模拟分光光度法在增效联磺片分析中应用的研究

本文应用统计模拟分光光度法建立了同时测定增效联磺片三组分含量的分析方法。用全面交叉组合法安排实验，获得有限但足够的实验数据，再用逐步回归法构造在不同波长下吸光度与组分浓度经验关系的“最优”数学模型，用全组合检索法寻优求出未知样品诸组分的含量。为认证此方法用均匀设计安排回收率试验，并对含量测定结果进行了方差分析，结果均令人满意．     

Variation in likelihood ratios for forensic evidence evaluation of XTC tablets comparison

In forensic comparison casework, where it is investigated whether items are from the same source, the likelihood ratio (LR) is a measure for evaluating the strength of evidence of the observed (dis)similarity between these items. The paper concentrates on evaluation of various LR models for comparison of XTC tablets from different production batches. Starting from a two‐level random effect model, where means are considered random, the distribution of these means may be assumed normal or approximated by kernel density estimations (KDEs), and variation in the data may or may not be allowed to differ per batch. It is investigated what effect the corresponding model and estimation choices have on the distribution of LRs for same‐ and different‐batch comparisons. Copyright © 2010 John Wiley & Sons, Ltd.     

Spectrophotometric Determination of Methandienone in Tablets Using 1.4-Dihydrazinophthalazine

Abstract

A simple and sensitive method for the determination of methandienone in tablets using 1.4-dihydrazinophthalazine as the reagent is presented. The yellow coloured dihydralazinhydrazone shows the maximum at 401 nm and ntclar absorptivity of 1.5×10⁴ 1 mol^?1 cm^?1. Beer's law is obeyed up to 16 μ/mI methandienone. The method applied for the assay of methandienone in dosage form gave precise and reproducible results; recovery was 98.5% and relative standard deviation was 1. 5%.     

高效液相色谱-氢化物发生-原子荧光光谱法检测牛黄解毒片中的砷

采用高效液相色谱-氢化物发生-原子荧光光谱法(HPLC-HG-AFS)测定了牛黄解毒片中AsIII和AsV的含量,制定了牛黄解毒片中砷的质量控制标准;对砷的提取、分离和分析条件进行了优化.结果表明,在优化的提取、分离和分析条件下,牛黄解毒片中的AsⅢ和AsV分离良好,测定精密度和准确度较高;5个不同厂家生产的牛黄解毒片中均含有AsⅢ和AsV,所有厂家生产的牛黄解毒片中AsⅢ的含量均比AsV的含量高.     

Pharmaceutical polymorphs quantified with transmission Raman spectroscopy

The quantification of polymorphs in dosage forms is important in the pharmaceutical industry. Conventional Raman spectroscopy of solid‐state pharmaceuticals may be used for this, but it has some limitations such as sub‐sampling and fluorescence. These problems can be mitigated through the use of transmission Raman spectroscopy (TRS). The efficacy of TRS measurements for the prediction of polymorph content was evaluated using a ranitidine hydrochloride test system. Four groups of ranitidine hydrochloride‐based samples were prepared: three containing form I and II ranitidine hydrochloride and microcrystalline cellulose (spanning the ranges 0–10%, 90–100% and 0–100% form I fraction of total ranitidine hydrochloride), and a fourth group comprising form I ranitidine hydrochloride (0–10%) spiked commercial formulation. Transmission and conventional Raman spectroscopic measurements were recorded from both capsules and tablets of the four sample groups. Prediction models for polymorph and total ranitidine hydrochloride content were more accurate for the tablet than for the capsule systems. TRS was found to be superior to conventional backscattering Raman spectroscopy in the prediction of polymorph and total ranitidine hydrochloride content. The prediction model calculated for form I content across the 0–100% range was appropriate for process control [ratio of prediction to deviation (RPD) equal to 14.62 and 7.42 for tablets and capsules, respectively]. The 10% range calibrations for both form I and total ranitidine hydrochloride content were sufficient for screening (RPDs greater than 2.6). TRS is an effective tool for polymorph process control within the pharmaceutical industry. Copyright © 2011 John Wiley & Sons, Ltd.     

Forced-degradation study of valdecoxib as bulk drug and in tablet formulation by HPTLC

A stability-indicating forced-degradation study of valdecoxib was conducted using high performance thin layer chromatography (HPTLC). It was used to analyze valdecoxib as bulk drug and as tablets. Undegraded valdecoxib was eluted with a retardation factor, Rf, of 0.56. Valdecoxib was forcibly degraded by exposure to alkali, acid, oxidation, and light, the greatest degradation occurring under basic conditions. Base-degraded valdecoxib gave an additional peak with an Rf value of 0.76. The calibration curve was linear in the range of 0.2-1 microg/microL with a correlation coefficient of 0.9952. Complete validation was carried out for precision (inter-day, intra-day, repeatability), accuracy, and robustness. All the data were analyzed statistically. This HPTLC procedure shows the reliability needed for use as a stability-indicating method. It can quantify valdecoxib in bulk and in tablets and also resolves the degraded peak of valdecoxib. This method is also useful for studying the degradation pattern and degradation mechanism of valdecoxib.     

Stability Indicating Reversed-Phase High Performance Liquid Chromatography Method for Determination of Impurities in Ofloxacin Tablet Formulations

A gradient reversed-phase high performance liquid chromatography (RP-HPLC) method was developed for separation and quantitation of impurities in pharmaceutical dosage form of ofloxacin tablets. The developed method was a stability indicating test method for estimation of related impurities generated during synthesis, formulation, and storage of ofloxacin tablets. Forced degradation studies were performed on ofloxacin tablets including acid hydrolysis (5.0 M hydrochloric acid), base hydrolysis (5.0 M sodium hydroxide), oxidation (30% hydrogen peroxide), heat (105°C) humidity degradation 25°C/92% RH/119 b & 40 min, and photolytic degradation (2600 Lux/119 h & 40 min). From the degradation study, the degradation was found between 0–15%. Limit of detection and limit of quantification were established in terms of percentage for all potential impurities. The recovery studies were conducted on finished dosage samples (tablets) for all potential impurities and the average percentage recovery was ranged from 90.8 to 104.2. Placebo interference was verified by taking the placebo (composition of excipients) equivalent to weight in portion of test preparation and no interference was observed. The method was validated and found to be linear, accurate, precise, specific, robust, and reliable. The developed method was established in accordance to ICH guidelines.