Thermodynamic and Thermomicroscopy Study of Atorvastatin Calcium-Succinic Acid Binary Mixtures

Yudi Wicaksono; Budipratiwi Wisudyaningsih; Frida Oktaningtias Widiarthi; Tri Agus Siswoyo

doi:10.22146/ijc.25089

Thermodynamic and Thermomicroscopy Study of Atorvastatin Calcium-Succinic Acid Binary Mixtures

https://doi.org/10.22146/ijc.25089

Yudi Wicaksono^(1*), Budipratiwi Wisudyaningsih⁽²⁾, Frida Oktaningtias Widiarthi⁽³⁾, Tri Agus Siswoyo⁽⁴⁾

(1) Faculty of Pharmacy, University of Jember, Jl. Kalimantan I/2, Jember 68121, Indonesia
(2) Faculty of Pharmacy, University of Jember, Jl. Kalimantan I/2, Jember 68121, Indonesia
(3) Center for Development of Advanced Science and Technology, University of Jember, Jl. Kalimantan No. 37, Jember 68121, Indonesia
(4) Faculty of Agriculture, University of Jember, Jl. Kalimantan No. 37, Jember 68121, Indonesia
(*) Corresponding Author

Abstract

Binary mixtures of pharmaceuticals significantly affect the physical and chemical properties of each component. The aim of this work was to explore the thermal behavior and solid state transformation of binary mixture of atorvastatin calcium and succinic acid. The thermodynamics of binary mixtures of atorvastatin calcium - succinic acid were determined by differential scanning calorimeter. Meanwhile, thermomicroscopy and microstructure were determined by a polarized microscope equipped with a heating stage and camera. The results showed that melting points of atorvastatin calcium and succinic acid respectively were 159.35 and 188.51 °C. The solid-liquid phase diagram of atorvastatin calcium - succinic acid indicates the existence of two eutectic points at 136.57 °C and 120.96 °C respectively on the mole fraction of atorvastatin calcium 0.3 and 0.5. Tamman diagram accurately shows mole fraction of atorvastatin calcium at eutectic point 0.33 and 0.46 respectively for eutectic points 130.0 °C and 134.0 °C. Determination of Jackson’s roughness parameter showed a value of atorvastatin calcium, succinic acid and eutectic mixtures > 2 which indicates that the interfaces of remelting crystals were smooth. Microstructure of remelting crystal of atorvastatin calcium and succinic acid respectively was irregular form and crossed plates. The results of thermomicroscopy of binary mixtures of atorvastatin calcium-succinic acid were consistent with differential scanning calorimetry curves and solid-liquid phase diagram.

Keywords

thermodynamic; atorvastatin calcium; binary mixtures; phase diagram

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References

[1] Klimová, K., and Leitner J., 2012, DSC study and phase diagrams calculation of binary systems of paracetamol, Thermochim. Acta, 550, 59–64.

[2] Trache, D., Khimeche, K., Benelmir, R., and Dahmani, A., 2013, DSC measurement and prediction of phase diagrams for binary mixtures of energetic materials’ stabilizers, Thermochim. Acta, 565, 8–16.

[3] Meltzer, V., and Pincu, E., 2012, Thermodynamic study of binary mixture of citric acid and tartaric acid, Cent. Eur. J. Chem., 10 (5), 1584–1589.

[4] Vitez, I.M., and Newman, A.W., 2007, Thermal Analysis of Pharmaceuticals, CRC Press, Boca Raton, 222–260.

[5] Rao, S.K., Prasad, T., Mohanta, G.P., and Manna, P.K., 2011, An overview of statins as hypolipidemic drugs, Int. J. Pharm. Sci. Drug Res., 3 (3),178–183.

[6] Shayanfar, A., Ghavimi, H., Hamishehkar, H., and Jouyban, A., 2013, Coamorphous atorvastatin calcium to improve its physicochemical and pharmacokinetic properties, J. Pharm. Pharm. Sci., 16 (4), 577–587.

[7] Chadha, R., Kuhad, A., Arora, P., and Kishor, S., 2012, Characterisation and evaluation of pharmaceutical solvates of atorvastatin calcium by thermoanalytical and spectroscopic studies, Chem. Cent. J., 6 (1), 114–129.

[8] Shevchenko, A., Bimbo, L.M., Miroshnyk, I., Haarala, J., Jelínková, K., Syrjänen, K., van Veen, B., Kiesvaara, J., Santos, H.A., and Yliruusi, J., 2012, A new cocrystal and salts of itraconazole: Comparison of solid-state properties, stability and dissolution behavior, Int. J. Pharm., 436 (1-2), 403–409.

[9] Setyawan, D., Sari, R., Yusuf, H., and Primaharinastiti, R., 2014, Preparation and characterization of artesunate-nicotinamide cocrystal by solvent evaporation and slurry method, Asian J. Pharm. Clin. Res., 7 (Suppl. 1), 62–65.

[10] Zhang, H.X., Wang, J.X., Zhang, Z.B., Le, Y., Shen, Z.G., and Chen, Z.F., 2009, Micronization of atorvastatin calcium by antisolvent precipitation process, Int. J. Pharm., 374 (1-2), 106–113.

[11] Patel, J.R., Carlton, R.A., Needham, T.E., Chichester, C.O., and Vogt, F.G., 2012, Preparation, structural analysis, and properties of tenoxicam cocrystals, Int. J. Pharm., 436 (1-2), 685–706.

[12] Ober, C.A., and Gupta, R.B., 2012, Formation of itraconazole-succinic acid cocrystals by gas antisolvent cocrystallization, AAPS PharmSciTech, 13 (4), 1396–1406.

[13] Yamashita, H., Hirakura, Y., Yuda, M., Teramura, T., and Terada, K., 2012, Detection of cocrystal formation based on binary phase diagrams using thermal analysis, Pharm. Res., 30 (1), 70–80.

[14] Stoler, E., and Warner, J.C., 2015, Non-covalent derivatives: Cocrystals and eutectics, Molecules, 20 (8), 14833–14848.

[15] Górniak, A., Wojakowska, A., Karolewicz, B., and Pluta, J., 2011, Phase diagram and dissolution studies of the fenofibrate–acetylsalicylic acid system, J. Therm. Anal. Calorim., 104 (3), 1195–1200.

[16] Rao, V.P.R., Somannavar, Y.S., Kumar, N.S., Reddy, S.B., Islam, A., and Babu, B.H., 2011, Preparation of stable new polymorphic form of atorvastatin calcium, Pharm. Lett., 3 (5), 48–53.

[17] Chadha, R., Arora, P., Bhandari, S., and Bala, M., 2012, Current Microscopy Contributions to Advances in Science and Technology, Formatex Research Center, Badajoz, 1013–1024.

DOI: https://doi.org/10.22146/ijc.25089