Thermal hazards of cracker mixture using DSC

DSC studies of cracker mixtures of different compositions of potassium nitrate, sulphur and aluminum have shown some critical characteristics either with the increase or decrease in the composition of the components. Specifically, sulphur composition below 8% showed no exothermic activity. The studies revealed that a minimum of 11% to a maximum of 17% of sulphur is required for good cracking characteristics. The kinetics of decomposition of cracker mixture is carried out employing DSC multiple heating rate kinetic method. Increase in sulphur content decrease the energy of activation facilitating easy ignition of the cracker mixtures. Arrhenius parameters for cracker mixture decomposition are reported in this paper.     

Investigation of the Compatibility of a Multi-Component TN Liquid Crystal Mixture and a Multi-Component Cholesteric Liquid Crystal Mixture by DSC

The phase transition curves of a multi-component TN liquid crystal mixture (TN 88-1) and a multi-component cholesteric liquid crystal mixture (Ch 88-2) were plotted by using a differential scanning calorimeter. The phase transition temperature and phase transition heat were obtained from the DSC curves. The results show that the components of TN 88-1 are compatible and they can form a stable mixture with CB 15 chiral liquid crystal. The components of Ch 88-2 are not compatible and Poly (MMA-BMA) can greatly improve their compatibility. This revised version was published online in July 2006 with corrections to the Cover Date.     

Interaction study between pefloxacin mesilate and some diluents using DSC supported with isothermal method

The present investigation was carried out to screen compatibility of some diluents with pefloxacin mesilate using differential scanning calorimetry (DSC), isothermal stability studies, along with stability studies in liquid state and to assign relative ranking to diluents. Compatibility was predicted with MCC101, MCC102, DCP anhydrous, Emcompress, while melting endotherm of drug was lost in admixtures of dextrose anhydrous, Pearlitol, Lactopress spray dried, Lactochem fine powder and Lycatab indicating possibility of interaction. Enthalpy changes were used for relative ranking of diluents.     

Comparison of Generic Hydrochlorothiazide Formulations by Means of TG and DSC Coupled to a Photovisual System

The compatibilities and stabilities of some binary mixtures and generic hydrochlorothiazide formulations were studied by using TG, DSC and a DSC-photovisual system. The kinetic parameters were determined via the Arrhenius equations. Tablet B presented higher compatibility and thermal stability than those of tablets A and C. The photovisual system demonstrated that the decomposition of tablet A occurs before the melting point, due to the Maillard reaction between the hydrochlorothiazide and lactose present in the formulation. The behaviour and rate constants of binary mixtures suggest that lactose can be substituted for microcrystalline cellulose, MC(101), in tablet A. The DSC and TG data revealed different characteristics of compatibility and stability in generic formulations from different manufacturers. This revised version was published online in July 2006 with corrections to the Cover Date.     

丁基橡胶阻尼材料相容性的DSC与DMA研究

高聚物力学阻尼材料是一种能消除振动和噪声以聚合物为基质的功能材料。当聚合物处于玻璃化转变温度(Tg)区域时,其链段运动不能完全跟上振动的速度而产生分子链内摩擦,吸收一部分振动能,再以“热”的形式而耗散,这样就起到减少振幅或降低振幅的作用。     

Multicomponent reaction design in the quest for molecular complexity and diversity

Multicomponent reactions have become increasingly popular as tools for the rapid generation of small-molecule libraries. However, to ensure sufficient molecular diversity and complexity, there is a continuous need for novel reactions. Although serendipity has always played an important role in the discovery of novel (multicomponent) reactions, rational design strategies have become much more important over the past decade. In this Review, we present an overview of general strategies that allow the design of novel multicomponent reactions. The challenges and opportunities for the future will be discussed.     

Determination of Meloxicam in Tablet Formulations by Ultraviolet Spectrophotometry and High-Performance Liquid Chromatography

ABSTRACT

Assay procedures based on UV spectrophotometry and high-performance liquid chromatography (HPLC) have been developed for the determination of meloxicam in tablet formulations. The HPLC method used a reversed-phase C18 column with 0.05M Tris acetic acid buffer - tetrabutylammonium reagent–acetonitrile as eluent, and UV detection at 360nm with isoxicam as the internal standard. The UV method was based on measuring an acidic solution of the drug at 341nm. A comparison was established in terms of linearity, sensitivity, precision, and accuracy. Both methods were simple and rapid. HPLC was more precise and more accurate, the UV technique was slightly faster.     

Preformulation compatibility studies of etamsylate and fluconazole drugs with lactose by DSC

Chemical compatibility of two drugs, namely, etamsylate and fluconazole was studied with lactose as excipient, employing differential scanning calorimetry (DSC) and X-ray diffraction (XRD) techniques. The DSC patterns recorded for the mixtures of both the drugs with the common excipient (lactose) indicated that fluconazole as well as etamsylate were incompatible with lactose at high temperatures. X-ray diffraction patterns recorded for pure drugs and lactose and the mixtures of individual drugs with lactose prepared at room temperature by intimate grinding of the components revealed incompatibility of both the drugs with lactose also at room temperature. This revised version was published online in July 2006 with corrections to the Cover Date.     

Drug-Excipient Compatibility Studies. Search of interaction indicators

This paper is the first one of a research project aimed to find and optimize methods by which drug-excipient compatibility can be reliably and quickly assessed. A number of experimental techniques (simultaneous TG-DSC, FT-IR spectroscopy, X-ray powder diffraction, scanning electron microscopy) have been used to investigate the compatibility between a novel tricyclic β-lactam antibiotic developed by GlaxoWellcome (now GlaxoSmithKline), GV118819x, and some commonly used excipients (poly(vinylpyrrolidone), magnesium stearate and α-lactose). Binary mixtures of two different compositions have been analyzed: drug:excipient=80:20 and 20:80 (mass/mass). Both qualitative and quantitative interaction indicators have been identified. It is shown that simultaneous thermal analysis is the best suited technique in the search of interaction indicators. With a proper selection of experimental conditions it is able to reveal the thermal changes brought about by the early stages of interaction, i.e. those occurring during the measurement on physical mixtures not previously annealed under stress conditions. Such an ability is discussed, in particular, with respect to the role of the water vapour, which has been found to be a critical parameter for all our systems. This revised version was published online in August 2006 with corrections to the Cover Date.     

Novel chemometric strategy based on the application of artificial neural networks to crossed mixture design for the improvement of recombinant protein production in continuous culture

The optimal blends of six compounds that should be present in culture media used in recombinant protein production were determined by means of artificial neural networks (ANN) coupled with crossed mixture experimental design. This combination constitutes a novel approach to develop a medium for cultivating genetically engineered mammalian cells. The compounds were collected in two mixtures of three elements each, and the experimental space was determined by a crossed mixture design. Empirical data from 51 experimental units were used in a multiresponse analysis to train artificial neural networks which satisfy different requirements, in order to define two new culture media (Medium 1 and Medium 2) to be used in a continuous biopharmaceutical production process. These media were tested in a bioreactor to produce a recombinant protein in CHO cells. Remarkably, for both predicted media all responses satisfied the predefined goals pursued during the analysis, except in the case of the specific growth rate (μ) observed for Medium 1. ANN analysis proved to be a suitable methodology to be used when dealing with complex experimental designs, as frequently occurs in the optimization of production processes in the biotechnology area. The present work is a new example of the use of ANN for the resolution of a complex, real life system, successfully employed in the context of a biopharmaceutical production process.     

Adsorption of BSA and Hemoglobin on Hydroxyapatite Support: Equilibria and Multicomponent Dynamic Adsorption

Interactions of Bovin Serum Albumin and Hemoglobin with an hydroxyapatite gel (HA-Ultrogel, Sepracor), have been studied separately in batch experiments. The adsorption isotherms are of the Langmuir type and can be used directly to scale column operations.For adsorption of hemoglobin alone, in column at pH 6.8 (equal to its isoelectric point) we notice that a classical intraparticle transfer model, based on a constant effective diffusion coefficient represents perfectly the symmetrical breakthrough curve. For acid pH values (pH 5.8), Langmuir isotherms of BSA and hemoglobin adsorptions showed a strong curvature, sign of a quite irreversible adsorption and breakthrough curves obtained under these conditions, exhibit a high dissymmetrical shape for both proteins. In that case, a model of diffusion based on the adsorption on two types of independent sites, with two intraparticle transfer coefficients, gives a good representation of the breakthrough for adsorption of both proteins separately.Binary mixtures of these components were prepared and injected in columns packed with the same support. Competitive Langmuir equation, based on the results obtained in monocomponent batch experiments, give a very good fit to our system. The intraparticle transfer in that case seems to be facilitated, and one effective coefficient alone is enough to predict the breakthrough curves obtained. This behaviour may be the result of an increase of the solution ionic strength, and of the smaller irreversibility feature of the adsorption when proteins are in competition.     

DSC Studies of the Effects of Cisplatin and Transplatin on G-Actin

The effects of cisplatin and its trans isomer transplatin on the thermal denaturation of G-actin were studied with a Micro DSC-III differential scanning calorimeter. The denaturation enthalpy of G-actin was found to be 12 J g^–1, and the denaturation temperature was 328 K. The thermal denaturation curve showed that increasing cisplatin concentration decreased the enthalpy change. However, after the ratio of cisplatin to G-actin attained 8:1 (mol:mol), the denaturation enthalpy no longer decreased. Transplatin decreased the enthalpy change more rapidly. In contrast with cisplatin, the denaturation peak at 328 K disappeared, and a strong exothermic peak appeared at 341 K when the ratio of transplatin to G-actin was 8:1 (mol:mol). The enthalpy change was 75 J g^–1, which is far in excess of the range of weak interactions. This strong exothermic phenomenon probably reflects the agglutination of protein. The effects of cisplatin and transplatin on the number of the free thiol groups of G-actin are discussed.This revised version was published online in November 2005 with corrections to the Cover Date.     

DSC Studies on Melting and Crystallization of Polyamide 6/Biopol Blends

Blends obtained from Biopol D600G and polyamide 6 reveal in DSC investigations multiphase structure with a distinct crystalline polyamide 6 phase. Due to rapid crystallization of the polyamide 6 the crystallization of the Biopol D600G is retarded. The grade of crystallization of Biopol D600G is lower in the blends than in the pure state, as calculated from the melting enthalpies. Crystallization of polyamide 6 in the blends is faster and results in increasing of the grade of crystallization of polyamide 6 phase comparing to the unblended component. This revised version was published online in August 2006 with corrections to the Cover Date.     

水分子凝胶聚集态的DSC和AFM研究

合成了一种新型凝胶因子，能在很低的浓度下使水发生凝胶化，形成水分子凝 胶。通过原子力显微镜(AFM)以及透射电子显微镜(TEM)对水分子凝胶的微观形态进 行了表征，表明凝胶因子可以在水中聚集、自组装成延伸的螺旋缠绕细纤维结构， 并且得出了纤维束的平均直径在100nm左右，平均孔径在100nm左右。利用示差扫描 量热(DSC)的数据，计算了水分子凝胶体系的平均孔径大小在50～100nm左右，与 AFM和TEM观测的结果较吻合，从而验证了DSC理论推导计算的正确性。同时还得到 了不同浓度的水分子凝胶的凝胶—溶胶相转变温度Tcs在55—72℃之间，而且随着 凝胶因子浓度的增加，水分子凝胶体系的平均孔径呈减小的趋势，凝胶—溶胶相转 变温度呈上升的趋势。     

Application of DSC and NIRS to study the compatibility of metronidazole with different pharmaceutical excipients

The purpose of the present work was to study the compatibility of metronidazole with different pharmaceutical excipients (hydroxypropyl methylcellulose, poly(ethylene oxide), microcrystalline cellulose, dicalcium phosphate dihydrate, and anhydrous dicalcium phosphate) using differential scanning calorimetry and diffuse reflectance spectroscopy. Dicalcium phosphate dihydrate was the only excipient that showed interaction with metronidazole even before storage. Changes referring to a possible transition to dihydrate form were observed in the thermal curves of anhydrous dicalcium phosphate after four weeks of storage. Although dicalcium phosphate dihydrate can be replaced by the anhydrous form in pharmaceutical formulations, the observed transition might negatively influence the stability of dosage forms.     

Multicomponent Crystal of Metformin and Barbital: Design,Crystal Structure Analysis and Characterization

The formation of most multicomponent crystals relies on the interaction of hydrogen bonds between the components, so rational crystal design based on the expected hydrogen-bonded supramolecular synthons was employed to establish supramolecular compounds with desirable properties. This theory was put into practice for metformin to participate in more therapeutic fields to search for a fast and simple approach for the screening of candidate crystal co-formers. The prediction of intermolecular synthons facilitated the successful synthesis of a new multicomponent crystal of metformin (Met) and barbital (Bar) through an anion exchange reaction and cooling crystallization method. The single crystal X-ray diffraction analysis demonstrated the hydrogen bond-based ureide/ureide and guanidine/ureide synthons were responsible for the self-assembly of the primary structural motif and extended into infinite supramolecular heterocatemeric structures.     

EC/CA共混物的相容性和热稳定性

EC/CA共混物的相容性和热稳定性;乙基纤维素;醋酸纤维素;溶液共混;相容性     

Statistical mixture design optimization of extraction media and mobile phase compositions for the characterization of green tea

The influence of different solvents on the extraction medium and the RP-HPLC mobile phase composition were investigated by statistical mixture designs to optimize solvent proportions to prepare the fingerprint of a medicinal herbal extract. For modeling, the number of peaks was used as a measure of fingerprint information. The optimum compositions of solvent to extract chemical substances from green tea and for mobile phase chromatographic analysis were ethyl acetate/ ethanol/dichloromethane (20:5:75 v/v/v) and MeOH/ACN/water (7.5:57.5:35 v/v/v), respectively. This system results in 26 peaks in the chromatographic fingerprint. These results show that an incorrect choice of modifiers for mobile phase composition and solvent extraction hampers the detection of a maximum number of peaks and produces a poor chromatographic fingerprint.     

Optimization of sylvite transformation into arcanite using experimental design methodology

This study is an application of the experimental design methodology for optimizing a potassium sulfate synthesis reaction. The latter is a two‐stage reaction through an intermediate product (Schoenite: K₂SO₄.MgSO₄·6H₂O). To determine optimal experimental conditions of the first stage, we have conducted a fractional factorial design and a central composite one. The optimal conditions of the second stage were determined only by means of a fractional factorial design. Several physico‐chemical techniques were used to implement this study, namely potentiometry, complexometry, gravimetry and X‐ray diffraction. This work has showed that this double decomposition reaction, when performed under the determined optimal conditions, gives good quality potassium sulfate (purity more than 95%) with a maximal yield. Copyright © 2008 John Wiley & Sons, Ltd.     

How experimental design can improve the validation process. Studies in pharmaceutical analysis

A critical discussion about the possibility of improving the method validation process by means of experimental design is presented. The reported multivariate strategies concern the evaluation of the performance parameters robustness and intermediate precision, and the optimisation of bias and repeatability. In particular, accuracy and precision improvement constitutes a special subset of experimental design in which the bias and the relative standard deviation of the assay are optimised. D-optimal design was used in order to plan experiments for this aim. The analytical methods considered were capillary electrophoresis, HPLC, adsorptive stripping voltammetry and differential pulse polarography. All methods were applied to real pharmaceutical analysis problems.