Compatibility study between sitagliptin and pharmaceutical excipients used in solid dosage forms

Differential scanning calorimetry (DSC) is a primary technique for measuring the thermal properties of materials, which reflects the physico-chemical properties of drug substances. In the present study, it is used as a screening technique for assessing the compatibility of sitagliptin with some currently employed pharmaceutical excipients. The influence of processing conditions and their effects (simple blending, co-grinding or kneading) on drug stability was evaluated. Sitagliptin showed a sharp endothermic peak at 212.1 °C with an enthalpy change of 131.5 J g^?1 indicating melting of drug. Facile transformation of dehydrated sitagliptin to monohydrate form was observed in some mixtures, disappearance of sharp melting endothermic peak of sitagliptin was observed in some mixtures. On the basis of DSC results, sitagliptin was found to be compatible with micro crystalline cellulose, croscarmellose, and pregelatinized starch. Some excipient interaction was observed with magnesium stearate, ascorbic acid, and citric acid. X-ray diffractometry and FT-IR were used as supportive tools in interpreting the DSC results. Overall, the excipients selected were compatible with the API and the mixtures are stable within the tested conditions. These results would be useful for formulation development of the film coated tablets of sitaglitptin.     

Correlation and prediction of ternary excess enthalpy data

Methods for predicting ternary excess enthalpies from excess enthalpy data for the three binary mixtures involved are examined and tested for forty-two sets of ternary data. In order to study the relation between the performance of the methods and the characteristics of the components in the mixture, the sets of data were classified into four groups according to the chemical nature of their components. The asymmetric equations proposed by Scatchard, Toop, and Hillert are shown to provide accurate predictions. The ratio of the standard deviations between experimental and predicted excess enthalpies and the maximum absolute value of this magnitude is 0.05 or less for most of the systems. These equations are asymmetric with respect to the numbering of components. A rule is given for selecting which component is to be designated as component 1 for systems showing endothermic mixing, exothermic mixing, or a combination of endothermic and exothermic mixing. Correlation methods are also examined and a partial differential approximant is proposed to represent the ternary contribution to the excess enthalpy.     

The effect of various potato cultivars at different times during growth on starch content determined by DSC

Differential scanning calorimetry (DSC) was used to determine the starch content of potato dry matter isolated from various cultivars at different times during growth. When potato dry matter was heated in the presence of excess water, a symmetrical endothermic peak resulted, which was similar to the gelatinization peak of pure starch. From the enthalpy value of potato dry matter and pure potato starch at a moisture content of 70%, the starch content in the potato dry matter can be determined. Starch content increased as growth progressed to a maximum and then decreased. The effect of moisture content and sample mass on gelatinization of dry matter and starch was also investigated. Compared to other starch analysis technique, DSC is a simple and more rapid method.     

Ionization enthalpy of benzoic acid in water—dimethylsulfoxide mixtures

The ionization enthalpy of benzoic acid has been measured calorimetrically at 25°C in H₂ODMSO mixtures ranging from pure water to a maximum DMSO molar ratio X_DMSO = 0.80. With the increase of DMSO content, the ionization becomes more and more endothermic, and for X_DMSO = 0.8 the ionization enthalpy is about 6 kcal mol^?1 higher than in water. By also measuring the solution enthalpy of crystalline benzoic acid in the mixtures, it has been shown that the solvation of the undissociated molecule is the main cause for the increase of the dissociation enthalpy. A comparison has been made between the relative enthalpies of benzoic and hydroxide ions in H₂ODMSO mixtures.     

DSC analysis of Al6061 aluminum alloy powder by rapid solidification

Differential scanning calorimetry (DSC) is a powerful technique that measures the heat evolution from a sample under a controlled condition and studies the phase transformation, precipitation, and dissolution activities. In this work, we investigated the influence of admixed silicon and silicon carbide and the effect of different atmospheres on the heat flow properties and microstructure of atomized Al6061 powder using DSC and scanning electron microscopy. The DSC analysis revealed the addition of silicon considerably decreased the temperature of first endothermic peaks. With an increase in silicon content the enthalpy for the first endothermic peak increased, whereas the second endothermic peak decreased. An endothermic peak, indicating the formation of AlN, was observed for powders without the silicon addition, but was noticeably absent in the case of alloys with Si addition. The SiC addition has no influence on changing the enthalpy of the systems we investigated. The reason for this behavior is analyzed and presented in this article.     

Mischungsenthalpien von geschmolzenen Kupfer(I)-halogenid-Chalkogen Systemen

Enthalpies of Mixing of Liquid Copper(I)-Halide-Chalkogen Systems The integral enthalpies of mixing of liquid CuCl(Br)–Se(Te) mixtures were determined in an isoperibolic calorimeter at temperatures of 766 and 818 K for tellurium and 818 K for selenium mixtures. The selenium systems are endothermic, the tellurium systems exothermic. The absolute value of the enthalpy of mixing of the tellurium systems decreases with increasing temperatures. The endothermic resp. exothermic behaviour of these systems is interpreted in terms of the structure of these melts.     

Effects of electric fields in polymerization on enthalpy of PMAA anhydridization

PMAA (polymethacrylic acid) polymerized by γ-irradiation in electric field forms six-membered cyclic anhydride during heating process and the enthalpy of PMAA anhydridization was determined by DSC. Why the endothermic peak of PMAA anhydridization in DSC curve between 200 and 300 °C appears is particularly explained by calculation. The relations between applied electric field and the enthalpy of PMAA anhydridization are studied. The results show that, with the increases of the intensity of electric field in polymerization, the enthalpy of PMAA forming anhydrides nonlinearly increase, which might be related to orientation of carboxylic acid groups of the PMAA in an electric field.     

Wetting and adsorption on organophilic illites and swelling montmorillonites in methanol-benzene mixtures

Adsorption and immersion were studied simultaneously in methanol-benzene mixtures on non-swelling organophilic illites and swelling organophilic montmorillonites. From the combination of adsroption and calorimetric data, equations were proposed for the determination of the adsorption capacity and the molar enthalpies of wetting differences, if the adsorption layer behaved ideally. From the experimental enthalpy isotherms of wetting and the enthalpy functions related to the ideal behaviour of the layer, qualitative conclusions were drawn on the excess enthalpy of the adsorpition layer. It was again established that the adsorption layer composed of alkyl chains, benzene and methanol has a regular cluster structure in certain concentration ranges, which breaks at higher methanol concentrations. This change is reflected by a significant endothermic peak of the differential molar enthalpy.For the organophilic montmorillonites, the enthalpy of swelling was determined separately as a function of the composition. The non-swelling organophilic illites were chosen as a reference system.Dedicated to Professor Dr. Armin Weiss on the occassion of his 60th birthday.     

Thermal effects in polypropylene after high-pressure plastic deformation

Differential scanning calorimetry is employed to study thermal effects that are observed after plastic deformation of PP under pressures of 0.5–3.0 GPa. Thermograms demonstrate an exothermic peak at 149°C, which is related to cold crystallization, and an endothermic peak at 162°C, corresponding to melting. The enthalpies of phase transitions depend on pressure and the degree of deformation specified by the rotation angle of anvils. Pressure treatment is conducted with grounded and insulated anvils. The UV irradiation of samples treated under pressure diminishes the enthalpy of both thermal processes.     

Determination of optimum processing temperature for transformation of glyceryl monostearate

The purpose of this study was to clarify the mechanism of transformation from alpha-form to beta-form via beta'-form of glyceryl monostearate (GM) and to determine the optimum conditions of heat-treatment for physically stabilizing GM in a pharmaceutical formulation. Thermal analysis repeated twice using a differential scanning calorimeter (DSC) were performed on mixtures of two crystal forms. In the first run (enthalpy of melting: DeltaH1), two endothermic peaks of alpha-form and beta-form were observed. However, in the second run (enthalpy of melting: DeltaH2), only the endothermic peak of the alpha-form was observed. From a strong correlation observed between the beta-form content in the mixture of alpha-form and beta-form and the enthalpy change, (DeltaH1-DeltaH2)/DeltaH2, beta-form content was expressed as a function of the enthalpy change. Using this relation, the stable beta-form content during the heat-treatment could be determined, and the maximum beta-form content was obtained when the heat-treatment was carried out at 50 degrees C. An inflection point existed in the time course of transformation of alpha-form to beta-form. It was assumed that almost all of alpha-form transformed to beta'-form at this point, and that subsequently only transformation from beta'-form to beta-form occurred. Based on this aspect, the transformation rate equations were derived as consecutive reaction. Experimental data coincided well with the theoretical curve. In conclusion, GM was transformed in the consecutive reaction, and 50 degrees C was the optimum heat-treatment temperature for transforming GM from the alpha-form to the stable beta-form.     

Dielectric Study of Aqueous Solutions of Alanine and Phenylalanine

Dielectric relaxation measurements on aqueous solutions of alanine and phenylalanine were carried out using time domain reflectometry (TDR) at 25, 30, 35, and 40 °C in the frequency range from 10 MHz to 20 GHz. Aqueous solutions of alanine and phenylalanine are prepared for five different molar concentrations of the respective amino acid. For all the solutions considered, only one relaxation peak was observed in this frequency range. The relaxation peaks shift to lower frequency with an increase in alanine and phenylalanine molar concentration. The molar enthalpy of activation and molar entropy of activation show endothermic interactions.     

聚四氟乙烯等温稀释型量热计

过量焓是溶液的基本热力学性质,近廾年来不少学者对它进行了大量的研究,取得了引人注目的成绩。目前应用较多的为等温稀释型及流动型量热计。尽管后者具有速度快、试剂用量省等优点,但前者结构简单、操作方便和实验精度高,因此得到广泛的应用。传统的等温稀释型量热计的本体为玻璃杜瓦瓶,当活塞上下移动时常常引起破裂,另一方面由于使用汞封,使实验物料受到很大限制。为了克服这些缺点,我们用聚四氟乙烯作为量热计本体,取得满意的效     

Thermal, structural and rheological behaviour of native and modified waxy corn starch with hydrochloric acid at different temperatures

In this study, samples of native waxy corn starch, waxy corn starch treated with HCl 0.15 mol L^?1 at 20 and 50 °C, respectively, were analysed. The thermogravimetric curves showed similar behaviour with three main mass losses and a decrease in the thermal stability. The acid hydrolysis in low HCl concentration performed for 4 h caused a decrease in peak temperature (DSC), viscosity peak (RVA), gelatinisation enthalpy (DSC) and relative crystallinity (XRD), and an increase in the average roughness (NC-AFM). The X-ray diffraction patterns displayed the ‘A’ type for all the starch granules.     

A new approach for the estimation of the melting enthalpy of metastable crystalline compounds using differential scanning calorimetry

This article focuses on the development of an innovative method, based on thermodynamic considerations and with the use of Differential Scanning Calorimetry (DSC), for the estimation of the melting enthalpy of crystalline compounds which are metastable near their melting temperature. The curves obtained, at various heating rates, are analysed in two steps. In the first step, the area of a zone generated by the melting endothermic peak is calculated following a specific method. In the second step, the melting enthalpy is extracted from this area through an enthalpy balance. This method is applied to both identified crystallographic forms, named form I and form II, respectively, of Etiracetam (UCB Pharma). The results show that the melting enthalpy of the stable form II compare well with the ones obtained using conventional methods. The curves of the metastable form I present thermal instabilities (partial solid–solid polymorphic transition and beta-recrystallization) near the form I melting peak leading to difficulties for a direct determination of the melting enthalpy by conventional methods. The proposed method is therefore very useful for the estimation of the form I melting enthalpy.     

Studies of the enthalpy relaxation and the “multiple melting” behavior of semicrystalline poly(arylene ether ether ketone) (PEEk)

We report the results of an investigation by differential scanning calorimetry (DSC) of two mobility controlled processes in the amorphous phas e of semicrystalline PEEK — enthalpy relaxation below the glass transition (T _g) and secondary crystallization aboveT _g. Both result in the observation of an endothermic peak just above the annealing temperature in the DSC scan of the polymer — the enthalpy recovery peak and the low temperature melting peak, respectively. There is a striking similarity in the time and temperature dependence of the endothermic peak for these two processes. These results are reminiscent of those obtained from small strain creep studies of physical aging of semicrystalline PEEK below and aboveT _g.We gratefully acknowledge support of this work by the National Science Foundation, Science and Technology Center for High Performance Polymeric Adhesives and Composites under DMR grant 91-2004 and by an NSF Young Investigator Award (DMR 93-57512).     

内压与液体混合物的超额焓

本文在前文提出的通用液体混合模型的基础上, 对其中某些近似假设和混合规则进行了合理的修正, 从而得到了一个液体混合物的超额焓与组分内压间的关系式。对于正常液体混合物, 式中有两个可调的修正系数, 对于醇-烃混合物, 则有三个可调参数。对十六个二元液体混合物的计算结果表明, 关系式不仅能准确地描述一般液体混合物的超额焓随浓度的变化规律, 而且亦适用于具有S型H^E-x曲线的复杂液体混合物。     

Enthalpy changes upon dilution and ionization of poly(L-glutamic acid) in aqueous solutions

The enthalpy changes accompanying the dilution and ionization of poly(L-glutamic acid) in water have been measured at 25 degrees C for two degrees of polymerization (DP = 115 and DP = 480) at various degrees of ionization, alpha, for a concentration range from about 0.2 to 0.002 monomol/L. The heat of dilution displays an unusual dependence on the degree of ionization, which is in sharp contrast to the behavior of other weak carboxylic polyelectrolytes, such as poly(acrylic acid). The exothermic heat effects observed at low values of alpha become endothermic for the region where the helix-coil transition is most pronounced, and for high degrees of ionization, they are exothermic again. Evidently, an endothermic heat effect, produced by an additional conformational transition in the dilution process, is superimposed on the exothermic enthalpy of dilution, and it overweighs the latter in the region of alpha where the conformational transition is prevailing. The calorimetric titration curve, which gives the dependence of the heat of ionization, deltaH(i), on alpha, has a maximum and is typical for poly(carboxylic acids) which undergo pH-induced conformational transition, such as poly(methacrylic acid). The values of deltaH(i) obtained at two polymer concentrations indicate that the enthalpy of ionization depends on the polypeptide concentration.     

Thermal, rheological, and structural behaviors of natural and modified cassava starch granules, with sodium hypochlorite solutions

The use of chemically modified starches is widely accepted in various industries, with several applications. In this research, natural cassava starch granules were treated with standard sodium hypochlorite solution at 0.8, 2.0, and 5.0 g Cl/100 g starch. The native and modified starch samples were investigated by means of the following techniques: simultaneous thermogravimetry–differential thermal analysis, which allowed us to verify the thermal decomposition associated with endothermic or exothermic phenomena; and differential scanning calorimetry that was used to determine gelatinization enthalpy as well as the rapid viscoamylographic analysis that provided the pasting temperature and viscosity. By means of non-contact-atomic force microscopy method and X-ray powder patterns diffractometry, it was possible to observe the surface morphology, topography of starch granules, and alterations in the granules’ crystallinity.     

TRANSITION IN THE MELT OF FEP COPOLYMER

The nature of the transition in molten FEP copolymer was examined in relation to the enthalpy change, mechanical damping and melt viscosity. For a pre-heat-treated FEP copolymer sample a small endothermic peak appeared at 309—312 ℃in DSC trace with enthalpy change 0.03—0.05 cal/g. A peak was also detected in damping versus temperature curve at the same temperature range. The theological property of FEP copolymer melt was similar to that of liquid crystal, but no birefrigence was viewed in the melt. Therefore the transition was explained as the melting of small crystallites which persist in typical copolymer beyond its melting temperature. These crystallites can act as nuclei for crystallization upon cooling.     

Molecular-dynamics studies of binary mixtures of Lennard-Jones fluids with differing component sizes

Molecular-dynamics calculations have been carried out for six pure liquids and three binary mixtures of Lennard-Jones fluids with differing component sizes and attractive interactions. Internal energies, radial-distribution functions, velocity autocorrelation functions and self-diffusion coefficients have been calculated and are discussed together with our previous results. The three mixtures obey the Lorentz-Berthelot rules and show endothermic mixing. The excess internal energy ΔU^E of mixtures with equal-sized components is symmetrical with respect to the mole fraction, but those for mixtures of different-sized components become asymmetrical. A comparison is made between the present ΔU^E data and those for real mixtures.