ENHANCEMENT OF SOLUBILITY AND DISSOLUTION RATE OF TELMISARTAN BY TELMISARTAN-OXALIC ACID CO-CRYSTAL FORMATION

Authors

  • Fikri Alatas Faculty of Pharmacy, University of Jenderal Achmad Yani, Cimahi, 40521, Indonesia
  • Hestiary Ratih 1. School of Pharmacy, Institut Teknologi Bandung, jalan Ganesha 10, Bandung 40132, Indonesia 2. Faculty of Pharmacy, University of Jenderal Achmad Yani, Cimahi, 40521, Indonesia
  • Sundani Nurono Soewandhi School of Pharmacy, Institut Teknologi Bandung, Jalan Ganesha 10, Bandung 40132, Indonesia

Keywords:

Telmisartan, Oxalic acid, Co-crystal, Solubility, Dissolution

Abstract

Objective: Telmisartan (TMS), an angiotensin II receptor antagonist used for the prevention and treatment of hypertension has a very low solubility in water, so its dissolution rate is low. The aim of this study is to improve the water solubility and dissolution rate of TMS by telmisartan-oxalic acid (TMS-OXA) co-crystal formation.

Methods: Co-crystal was prepared by solvent-drop grinding and solvent evaporation methods with methanol as solvent. Initial characterization was performed by powder X-ray diffraction (PXRD). Co-crystal formation of TMS-OXA was also characterized by differential thermal analysis (DTA), Fourier transform infrared (FTIR) spectroscopy, polarized microscopy, and scanning electron microscope (SEM) photomicrograph. Solubility test was performed in water media at 25°C, whilst dissolution rate test was performed using the paddle method in 900 mL of pH 7.5 phosphate buffer solution at 37±0.5°C for 60 min.

Results: The PXRD patterns of TMS-OXA after both preparation methods were different from its starting components. There was no difference in the powder X-ray diffraction pattern between two preparation methods. The polarized photomicroscope and SEM photomicrograph showed the habit TMS-OXA co-crystal was a rhomboid shape. The solubility test showed the TMS-OXA co-crystal has 11.7 fold higher than pure TMS. The dissolution rate test showed that TMS-OXA co-crystal has percentage of TMS dissolved after 60 min higher than pure TMS.

Conclusion: The co-crystal TMS-OXA formation can increase the solubility and dissolution rate of TMS.

 

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References

Marasini N, Tran TH, Poudel BK, Cho HJ, Choi YK, Chi SC, et al. Fabrication and evaluation of pH-modulated solid dispersion for telmisartan by spray-drying technique. Int J Pharm 2013;441:424-32.

Zhong L, Zhu X, Luo X, Su W. Dissolution properties and physical characterization of telmisartan-chitosan solid dispersions prepared by mechanochemical activation. AAPS Pharm Sci Tech 2013;14(2):541-50.

Kane RN, Kuchekar BS. Preparation, physicochemical characterization, dissolution and formulation studies of telmisartan cyclodextrin inclusion complexes. Asian J Pharm 2010;1:52-9.

Kalia A, Poddar M. Solid Dispersions: an approach towards enhancing dissolution rate. Int J Pharm Pharm Sci 2011;3(4):9-19.

Jagadeesan R, Radhakrishnan M. Novel approaches in the preparation of solid dispersion on solubility: a review. Int J Pharm Pharm Sci 2013;5(3):1000-4.

Schultheiss N, Newman A. Pharmaceutical co-crystals and their physicochemical properties. Cryst Growth Des 2009;9(6):2950-67.

Desiraju GR. Supramolecular synthons in crystal engineerings-a new organic synthesis. Angew Chem Int Ed Engl 1995;34:2311-27.

Trask AV, Motherwell WDS, Jones W. Pharmaceutical cocrystallization: Engineering a remedy for caffeine hydration. Cryst Growth Des 2005;5:1013-21.

Bucar DK, Henry RF, Lou XC, Duerst RW, MacGillivray LR, Zhang GGZ. Co-crystals of caffeine and hydroxybenzoic acids composed of multiple supramolecular heterosynthons: screening via solution-mediated phase transformation and structural characterization. Cryst Growth Des 2009;9(4):1932–43.

Abourahma H, Urban JM, Morozowich N, Chan B. Examining the robustness of a theophylline co-crystal during grinding with additives. Cryst Eng Comm 2012;14:6163-9.

Zhang S, Rasmuson Ã…C. The theophylline-oxalic acid co-crystal system: solid phases, thermodynamics and crystallisation. Cryst Eng Comm 2012;14:4644-55.

Heiden S, Trobs L, Wenzel KJ, Emmerling F. Mechanochemical synthesis and structural characterisation of a theophylline-benzoic acid co-crystal (1:1). Cryst Eng Comm 2012;14:5128-9.

McNamara DP, Childs SL, Giordano J, Iarriccio A, Cassidy J, Shet MS, et al. Use of a glutaric acid co-crystal to improve oral bioavailability of a low solubility API. Pharm Res 2006;23:1888-97.

Jones W, Motherwell WDS, Trask AV. Pharmaceutical co-crystals: an emerging approach to physical property enhancement. MRS Bulletin 2006;31:875-9.

Trask AV, Motherwell WDS, dan Jones W. Solvent-drop grinding: green polymorph control of co-crystallisation. Chem Commun 2004;890-1.

Braga D, Grepioni F. Making crystals from crystals: a green route to crystal engineering and polymorphism. Chem Commun 2005;29:3635-45.

Shan N, Toda F, Jones W. Mechanochemistry and co-crystal formation: effect of solvent on reaction kinetics. Chem Commun 2002;2372-3.

Shanpui P, Goud NR, Khandavilli UBR, Nangia A. Fast dissolving curcumin co-crystals. Cryst Growth Des 2011;11:4135-45

Dinnebier RE, Sieger P, Nar H, Shankland K, David WIF. Structural characterization of three crystalline modifications of telmisartan by single crystal and high-resolution X-ray powder diffraction. J Pharm Sci 2000;89(11):1465-79.

Tanaka H. The kinetic study of thermal dehydration of oxalic acid dihydrate I: crystalline powder material. J Therm Anal 1984;29:1115-22.

Chadha R, Bhandari S, Haneef J, Khullar S, Mandal S. Cocrystals of telmisartan: characterization, structure elucidation, in vivo and toxicity studies. Cryst Eng Comm 2014;16:8375-89.

Published

01-03-2015

How to Cite

Alatas, F., H. Ratih, and S. N. Soewandhi. “ENHANCEMENT OF SOLUBILITY AND DISSOLUTION RATE OF TELMISARTAN BY TELMISARTAN-OXALIC ACID CO-CRYSTAL FORMATION”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 7, no. 3, Mar. 2015, pp. 423-6, https://mail.innovareacademics.in/journals/index.php/ijpps/article/view/4705.

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