Investigation of crystallization and salt formation of poorly water-soluble telmisartan for enhanced solubility

Park, Chulhun, Meghani, Nileshkumar M., Shin, Yongkwan, Oh, Euichaul, Park, Jun-Bom, Cui, Jing-Hao, Cao, Qing-Ri, Tran, TT-D, Tran, Ha Lien Phuong and Lee, Beom-Jin 2019, Investigation of crystallization and salt formation of poorly water-soluble telmisartan for enhanced solubility, Pharmaceutics, vol. 11, no. 3, doi: 10.3390/pharmaceutics11030102.

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Title Investigation of crystallization and salt formation of poorly water-soluble telmisartan for enhanced solubility
Author(s) Park, Chulhun
Meghani, Nileshkumar M.
Shin, Yongkwan
Oh, Euichaul
Park, Jun-Bom
Cui, Jing-Hao
Cao, Qing-Ri
Tran, TT-D
Tran, Ha Lien PhuongORCID iD for Tran, Ha Lien Phuong
Lee, Beom-Jin
Journal name Pharmaceutics
Volume number 11
Issue number 3
Total pages 16
Publisher MDPI
Place of publication Basel, Switzerland
Publication date 2019-02-28
ISSN 1999-4923
Keyword(s) drug crystallinity
poorly water-soluble drug
salt formation
solubility enhancement
Summary The crystal changes and salt formation of poorly water-soluble telmisartan (TEL) in various solvents were investigated for enhanced solubility, stability and crystallinity. Polymorphic behaviors of TEL were characterized by dispersing in distilled water, acetone, acetonitrile, DMSO, or ethanol using Method I: without heat and then dried under vacuum at room temperature; and Method II: with heat below boiling temperature, cooled at 5 °C, and then dried under vacuum at 40 °C. For salt formation (Method III), the following four powdered mixtures were prepared by dispersing in solution of hydrochloric acid (HCl) (pH 1.2), TEL/HCl; in simulated gastric fluid (pH 1.2 buffer), TEL/simulated gastric fluid (SGF); in intestinal fluid (pH 6.8 buffer), TEL/simulated intestinal fluid (SIF); or in NaOH (pH 6.8), TEL/NaOH, respectively, and then dried under a vacuum at room temperature. The structures of powdered mixtures were then studied using a field emission scanning electron microscope (FESEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), FTIR, ¹H nuclear magnetic resonance (¹H-NMR), and LC⁻MS. The solubility of TEL in powdered forms was performed in pH 6.8, pH 1.2, and distilled water. No polymorphic behaviors of TEL were observed in various solvents as characterized by FESEM, DSC, PXRD, and FTIR. However, the structural changes of powdered mixtures obtained from Method III were observed due to the formation of salt form. Moreover, the solubility of salt form (TEL/HCl) was highly increased as compared with pure TEL. There were no significant changes of TEL/HCl compared with TEL in the content assay, PXRD, DSC, and FTIR during stressed storage conditions at 40 °C/75% relative humidity (RH) for 4 weeks under the closed package condition. Therefore, the present study suggests the new approach for the enhanced stability and solubility of a poorly water-soluble drug via salt form.
Language eng
DOI 10.3390/pharmaceutics11030102
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2019, The Authors
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Document type: Journal Article
Collections: Faculty of Health
School of Medicine
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