NOVEL PHARMACEUTICAL COCRYSTAL OF TELMISARTAN AND HYDROCHLOROTHIAZIDE

CO-CRYSTALS

  • ALPANA KULKARNI Department of Pharmaceutics, Maeer’s Maharashtra Institute of Pharmacy, Pune, Maharashtra, India.
  • SWAPNIL SHETE Department of Pharmaceutics, Maeer’s Maharashtra Institute of Pharmacy, Pune, Maharashtra, India.
  • VISHAL HOL Department of Pharmaceutics, Maeer’s Maharashtra Institute of Pharmacy, Pune, Maharashtra, India.
  • RITESH BACHHAV Department of Pharmaceutics, Maeer’s Maharashtra Institute of Pharmacy, Pune, Maharashtra, India.

Abstract

Objective: Telmisartan (TEL), commonly used antihypertensive, is poorly soluble in water and has limited and variable bioavailability. Commercially, TEL is available as a single drug and in combination with hydrochlorothiazide (HYZ). Researchers have developed cocrystals of TEL with coformers, namely, oxalic acid, glutaric acid, and saccharin. An attempt was made to prepare the cocrystals of TEL with HYZ, an active pharmaceutical ingredient (API) itself so that both the APIs are available in a single tablet. The present study was aimed at enhancement in solubility of TEL by formation of its cocrystals.


Methods: The cocrystals of TEL with HYZ, in different stoichiometric ratios (1:0.5, 1:1, and 1:2), were prepared by solvent coevaporation and liquid-assisted grinding methods. The cocrystals, consisting of TEL:HYZ (in 1:0.5 ratio and 1:1 ratio), depicted maximum yield, drug content, saturation solubility, and flow properties. These cocrystals were characterized by X-ray analysis, infrared spectroscopy, and thermal analysis.


Results: The crystal structure of TEL-HYX revealed that it was a cocrystal, since no proton was transferred between the TEL and HYZ molecules. It was predicted that two molecules are associated through a hydrogen bond between an acidic group of TEL and sulfonamido group of HYZ. The cocrystallization improved the solubility of TEL 7 times. In vitro release rate of tablets of cocrystals was higher than that of marketed TEL tablets. HYZ has a potential to form the cocrystals of TEL.


Conclusion: The objective of improvement in the solubility of TEL was successfully achieved by the formation of cocrystals of TEL: HYZ.

Keywords: Telmisartan, Cocrystal, Hydrochlorothiazide, Hydrogen bond, Dissolution

References

1. Jones W, Motherwell WD, Trask AV. Pharmaceutical co-crystals: An emerging approach to physical property enhancement. MRS Bull Pharm Mater Sci 2006;31:875-79.
2. Sekhon BS. Pharmaceutical co-crystals-a review. ARS Pharm 2009; 3:99-117.
3. Demiralay EC, Cubuk B, Ozkan SA, Alsancak G. Combined effect of polarity and pH on the chromatographic behavior of some angiotensin II receptor antagonists and optimization of their determination in pharmaceutical dosage forms. J Pharm Biomed Anal 2010;53:475-82.
4. Nakatani M, Takeshi S, Ohki T, Toyoshima K. Solid Telmisartan Pharmaceutical Formulations, US Patent No. 8980870B2; 2015.
5. Rossi R, Bellina F, Cauteruccio S, Castaldi G. A Process for the Preparation of Telmisartan, European Patent No. 2149566A1; 2019.
6. Rath S, Gupta BK, Bala NN, Dhal HC. Formulation and optimization of immediate release telmisartan tablets using full factorial design. Int J Appl Pharm 2011;3:20-4.
7. Kolatkar G, Zisman E. Pharmaceutical Compositions of Telmisartan, WO Patent No. 2007061415A1; 2008.
8. Kohlrausch A. Telmisartan Sodium Salt Pharmaceutical Formulation, US Patent No. 9029363 B2; 2003.
9. Donsbach K, Hof I. Crystalline Sodium Salt of Telmisartan and the Use of the Same as an Angiotensin Antagonist, WO Patent No. 2003037876 A1; 2001.
10. Wizel S, Perlman N, Avhar-Maydon S, Gilboa E. Amorphous and Polymorphic Forms of Telmisartan Sodium, WO Patent No. 2006/050509 A2; 2005.
11. Zupancic S, Smrkolj M, Stropnik T, Vrbinc M, Osolnik R, Sedmak G. Preparation of Telmisartan Salts, WO Patent No. 2007147889 A2; 2006.
12. Antoncic L, Copar A. Preparation of Telmisartan Salts with Improved Solubility, WO Patent No. 2006050921 A2; 2004.
13. Lee HW, Kang LH, Yoo CL, Kang SK, Lee SU, Ryuet HH. The New Telmisartan Zinc Salt and the Preparation, WO Patent No. 2010053233 A1; 2008.
14. Maneem V, Suryadevara V, Doppalapudi S. Formulation and evaluation of telmisartan solid dispersions using Entada scandens seed starch and poloxamer-188 as superdisintegrants. Asian J Pharm Clin Res 2018;11:474-81.
15. KunamV, Garikapati DR, Suryadevara V, Mandava VB, Janga RB, Sunkara SP. Solubility and dissolution rate enhancement of telmisartan by solid dispersion and pelletization techniques using soluplus as carrier. Int J Appl Pharm 2020;12:50-8.
16. Sood N, Khatry S, Arora S. Enhancement of dissolution of telmisartan by surface solid dispersion technique. J Pharm Res 2012;11:142-9.
17. Enose AA, Dasan P, Sivaramakrishanan H, Kakkar V. Formulation, characterization and pharmacokinetic evaluation of telmisartan solid dispersions. J Mol Pharm Org Process Res 2016;4:131-8.
18. Sekar V, Chellan VR. Immediate release tablets of telmisartan using superdisintegrant-formulation, evaluation and stability studies. Chem Pharm Bull (Tokyo) 2008;56:575-7.
19. Wani SU, Gangadharappa HV, Ashish NP. Formulation, development and characterization of drug delivery systems based telmisartan encapsulated in silk fibroin Nanosphere’s. Int J Appl Pharm 2019;11:247-54.
20. Yadav U, Chowdhuri AR, Sahu SK, Husain N, Rehman Q. Formulation of nanoparticles of telmisartan incorporated in carboxymethylchitosan for the better drug delivery and enhanced bioavailability. Asian J Pharm Clin Res 2017; 10:236-41.
21. Soni GC, Prajapati SK. Development and evaluation of self-nanoemulsifying drug delivery system for telmisartan. Int J Pharm Sci Res 2017;8:3948-61.
22. Patel J, Kevin G, Patel A, Raval M, Sheth N. Design and development of a self-nanoemulsifying drug delivery system for telmisartan for oral drug delivery. Int J Pharm Investig 2011;1:112-8.
23. Chadha R, Bhandari S, Haneef J, Khullarb S, Mandal S. Co-crystals of telmisartan: Characterization, structure elucidation, in vivo and toxicity studies. Cryst Eng Comm 2014;36:1-38.
24. Alatas F, Ratih H, Soewandhi SN. Enhancement ofsolubility and dissolution rate of tel by tel-oxalic acid co-crystal formation. Int J Pharm Pharm Sci 2015;7:423-6.
25. Sica DA. Rationale for fixed-dose combinations in the treatment of hypertension: The cycle repeats. Drugs 2002;62:443-62.
26. An Application to Include Blood Pressure Lowering Drug Fixed dose Combinations to the Model List of Essential Medicines Lists for the Treatment of Essential Hypertension in Adults. Available from: https:// www.who.int/selection_medicines/committees/expert/22/s12_fdc-antihypertensives.pdf?ua=1.
27. Indian Pharmacopoeia Commission. Indian Pharmacopoeia Volume I, Volume II, Volume III. Government of India Ministry of Health and Family Welfare. 6th ed. Ghaziabad: Indian Pharmacopoeia Commission; 2010.
28. Remington E. The Science and Practice of Pharmacy. 21st ed., Vol. 1. Philadelphia, PA: Lippincott Williams and Wilkins, University of the Sciences in Philadelphia; 2005.
29. Childs SL, Hardcastle KI. Co-crystals of piroxicam with carboxylic acids. Cryst Growth Des 2007;7:1291-304.
30. Sanphui P, Goud NR, Khandavilli UB, Nangia A. Fast dissolving curcumin co-crystals. Cryst Growth Des 2011;11:4135-45.
31. Trask AV, Motherwell WD, Jones W. Pharmaceutical co-crystallization: Engineering a remedy for caffeine hydration. Cryst Growth Des 2005;5:1013-21.
32. Abourahma H, Urban JM, Morozowich N, Chan B. Examining the robustness of a theophylline co-crystal during grinding with additives. CrystEngComm 2012;14:6163-9.
33. Zhang S, Rasmuson AC. The theophylline-oxalic acid co-crystal system: Solid phases, thermodynamics and crystallization. CrystEngComm 2012;14:4644-55.
34. Heiden S, Trobs L, Wenzel KJ, Emmerling F. Mechanochemicalsynthesis and structural characterization of a theophylline-benzoic acid co-crystal (1:1). CrystEngComm 2012;16:5128-9.
Statistics
106 Views | 137 Downloads
Citatons
How to Cite
KULKARNI, A., S. SHETE, V. HOL, and R. BACHHAV. “NOVEL PHARMACEUTICAL COCRYSTAL OF TELMISARTAN AND HYDROCHLOROTHIAZIDE”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 13, no. 3, Jan. 2020, pp. 104-12, doi:10.22159/ajpcr.2020.v13i3.36541.
Section
Original Article(s)