Solid-state compatibility studies of a drug without melting point

Veiga, Andressa; Oliveira, Paulo Renato de; Bernardi, Luana; Mendes, Cassiana; Silva, Marcos A. S.; Sangoi, Maximiliano S.; Janissek, Paulo Roberto; Murakami, Fábio S.

doi:10.1007/s10973-017-6756-8

Cited by 15 publications

(8 citation statements)

References 29 publications

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“…The purity was determined using aluminum crucibles with approximately 2.0 mg of sample at a heating rate of 2 °C min −1 from 30 °C to 400 °C. The purity of the sample was measured in triplicate using TASYS software (version 1.14, Shimadzu ® ), based on the Van’t Hoff equation:X2=false(To−Tmfalse)ΔHfRTo2 where the purity is determined from the molar percentage of impurities present in the sample, X 2 represents the mole fraction of impurities, T m is the sample melting temperature, T o is the melting point of the pure substance (°K), R is a gas constant and Δ H f is the heat of fusion of the main component (J mol −1 ) [14,15].…”

Section: Methodsmentioning

confidence: 99%

Solid-State Characterization of Different Crystalline Forms of Sitagliptin

et al. 2019

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Sitagliptin is an inhibitor of the enzyme dipeptidyl peptidase-4, used for the treatment of type 2 diabetes mellitus. The crystal structure of active pharmaceutical solids determines their physical and chemical properties. The polymorphism, solvates and hydrates can influence the free energy, thermodynamic parameters, solubility, solid-state stability, processability and dissolution rate, besides directly affecting the bioavailability. Thus, the physicochemical characterization of an active pharmaceutical ingredient is required to guarantee the rational development of new dosage forms. In this context, we describe herein the solid-state characterization of three crystalline forms of sitagliptin: sitagliptin phosphate monohydrate, sitagliptin phosphate anhydrous and sitagliptin base form. The investigation was carried out using differential scanning calorimetry (DSC), thermogravimetry (TG)/derivative thermogravimetry (DTG), spectroscopic techniques, X-ray powder diffraction (XRPD) and morphological analysis by scanning electron microscopy. The thermal analysis revealed that during the dehydration of sitagliptin phosphate monohydrate (Tpeak = 134.43 °C, ΔH = −1.15 J g−1) there is a characteristic crystalline transition event, which alters the physicochemical parameters of the drug, such as the melting point and solubility. The crystalline behavior of sitagliptin base form differs from that of sitagliptin phosphate monohydrate and sitagliptin phosphate anhydrous, mainly with regard to the lower temperature of the fusion event. The melting point (Tpeak) values obtained were 120.29 °C for sitagliptin base form, 206.37 °C for sitagliptin phosphate monohydrate and 214.92 °C for sitagliptin phosphate anhydrous. In relation to the thermal stability, sitagliptin phosphate monohydrate and sitagliptin phosphate anhydrous showed a slight difference; however, both are more thermostable than the base molecule. Therefore, through this study it was possible to establish the most suitable crystalline form of sitagliptin for the development of a safe, effective and appropriate pharmaceutical dosage form.

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Section: Methodsmentioning

confidence: 99%

Solid-State Characterization of Different Crystalline Forms of Sitagliptin

et al. 2019

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“…Furthermore, after the binary mixing of two ingredients, shifts in the transition temperature and peak shape and area invariably occur without necessarily representing a harmful interaction, so these changes need to be carefully evaluated [5]. Moreover, in the case of APIs that decompose without melting, omeprazole sodium for example, the search for incompatibility is problematic [6]. So the application of an unsupervised, multivariate statistical approach to improve the interpretation of DSC curves in the context of predicting the incompatibility in pharmaceutical mixtures is highly recommended.…”

Section: Introductionmentioning

confidence: 99%

DSC supported by factor analysis as a reliable tool for compatibility study in pharmaceutical mixtures

Rojek

Wesołowski

2019

J Therm Anal Calorim

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A chemometrically optimized DSC interpretation was developed for the identification of compatibility/incompatibility between active pharmaceutical ingredients (APIs) and excipients in pharmaceutical preparations. The chemometric approach based on factor analysis (FA) can be used as a supplementary tool for incompatibility detection in theophylline mixtures with excipients. The FA results expose the formation of two distinctly separate clusters on the FA score scatter plots-in the case of mixtures with compatible ingredients, one cluster was formed by theophylline and mixtures with high API content, the second by excipient and mixtures with high excipient content. In the event of incompatibility, the DSC curves of binary mixtures differ from those of ingredients, and the FA score scatter plot displays one cluster consisting of some mixtures at different ratios and the other of remaining mixtures and both ingredients. In brief, FA proved the incompatibility of theophylline mixtures with arabic gum, glucose, sorbitol and sucrose. The application of FA can help to circumvent the misinterpretation of DSC data.

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“…Compatibility studies may identify important changes in a drug upon formulation, such as changes in melting point or glass transition. The effects of these changes can be characterized using DSC, TG, XPRD, FTIR and SEM [24]. Following the development of the proposed finished product, stability studies are required to ensure the quality of the product and to determine the shelf life and storage conditions [25].…”

Section: Introductionmentioning

confidence: 99%

Solid-State Characterization and Compatibility Studies of Penciclovir, Lysine Hydrochloride, and Pharmaceutical Excipients

et al. 2019

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The physical and chemical characterization of the solid-state properties of drugs and excipients is fundamental for planning new formulations and developing new strategies for the treatment of diseases. Techniques such as differential scanning calorimetry, thermogravimetry, X-ray powder diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy are among the most commonly used techniques for these purposes. Penciclovir and lysine are individually used to treat the herpes virus. As such, the development of a formulation containing both drugs may have therapeutic potential. Solid-state characterization showed that both penciclovir and lysine were crystalline materials with melting points at 278.27 °C and 260.91 °C, respectively. Compatibility studies of penciclovir and lysine indicated a possible interaction between these substances, as evidenced by a single melting point at 253.10 °C. The compatibility of several excipients, including ethylenediaminetetraacetic acid, cetostearyl alcohol, sodium lauryl sulphate, di-tert-butyl methyl phenol, liquid petrolatum, methylparaben, nonionic wax, paraffin, propylene glycol, and propylparaben, was evaluated in ternary (penciclovir-lysine-excipient) mixtures (1:1:1, w/w/w) to determine the optimal formulation. The developed formulation was stable under accelerated and ambient conditions, which demonstrated that the interaction between penciclovir and lysine was suitable for the development of a formulation containing both drugs.

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Solid-state compatibility studies of a drug without melting point

Cited by 15 publications

References 29 publications

Solid-State Characterization of Different Crystalline Forms of Sitagliptin

Solid-State Characterization of Different Crystalline Forms of Sitagliptin

DSC supported by factor analysis as a reliable tool for compatibility study in pharmaceutical mixtures

Solid-State Characterization and Compatibility Studies of Penciclovir, Lysine Hydrochloride, and Pharmaceutical Excipients

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