1. Analysis of chlorthalidone polymorphs in raw materials and tablets and the effect of forms I and II on the dissolution properties of drug products.
- Author
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Bonfilio R, Leal JS, Santos OM, Pereira GR, Doriguetto AC, and de Araújo MB
- Subjects
- Antihypertensive Agents analysis, Chemistry, Pharmaceutical, Chlorthalidone analysis, Chromatography, High Pressure Liquid, Powders, Quality Control, Reference Standards, Solubility, Solvents, Spectrophotometry, Infrared, Tablets, X-Ray Diffraction, Antihypertensive Agents chemistry, Chlorthalidone chemistry, Drug Compounding
- Abstract
Chlorthalidone (CTD) is an antihypertensive drug and exhibits four crystalline forms: I, II, III and IV. In this paper, the incidence of CTD polymorphs in raw materials and in tablets as well as the solubility and dissolution properties of forms I and II have been studied. Raw materials were named as A, B, C, D, and E and tablets as Reference, G1, G2 and S. Using powder X-ray diffraction and infrared spectroscopy analyses we found that A, B, E, Reference and G1 contain CTD form I; C, D and S contain predominantly form II; and G2 contain a mixture of both forms. Solubility experiments showed that form II is up to 49% more soluble than form I and dissolution studies showed a significantly effect of the polymorphism on the dissolution of CTD from tablets. Based on these results, it was concluded that only the CTD form I is acceptable for preparation of tablet form. Moreover, we proposed the polymorphic quality control of CTD raw materials and tablets., (Copyright © 2013 Elsevier B.V. All rights reserved.)
- Published
- 2014
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