Analysis of chlorthalidone polymorphs in raw materials and tablets and the effect of forms I and II on the dissolution properties of drug products.
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.
Faculdade de Ciências Farmacêuticas, Universidade Federal de Alfenas (UNIFAL-MG), CEP 37130-000, Alfenas, MG, Brazil; Instituto de Ciências da Saúde, Universidade Federal de Mato Grosso (UFMT), CEP 78557-267, Campus Universitário de Sinop, Sinop, MT, Brazil. Electronic address: rudybonfilio@yahoo.com.br.
Rudy
R
Bonfilio
Jockastta S
JS
Leal
Olímpia M M
OM
Santos
Gislaine R
GR
Pereira
Antônio C
AC
Doriguetto
Magali B
MB
de Araújo
D000959:Antihypertensive Agents / Q000032:analysis / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D002752:Chlorthalidone / Q000032:analysis / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004339:Drug Compounding; D011208:Powders; D011786:Quality Control; D012015:Reference Standards; D012995:Solubility; D012997:Solvents; D013055:Spectrophotometry, Infrared; D013607:Tablets; D014961:X-Ray Diffraction
D000959:Antihypertensive Agents; D011208:Powders; D012997:Solvents; D013607:Tablets; D002752:Chlorthalidone
Attenued total reflection infrared spectroscopy; Chlorthalidone; Dissolution studies; Polymorphs; Powder X-ray diffraction