A new Febuxostat-Telmisartan Drug-Drug Cocrystal for Gout-Hypertension Combination Therapy.
J Pharm Sci
; 111(12): 3318-3326, 2022 12.
Article
em En
| MEDLINE
| ID: mdl-36028135
ABSTRACT
Drug-drug cocrystalllization is a novel mechanism for effective pharmacological combination therapy. In this work, we have demonstrated the preparation of a drug-drug cocrystal of a hypertension drug (Telmisartan; TEL) with a hyperuricemia drug (Febuxostat; FEB) in 11 molar ratio using a solvent evaporation method for the first time. Generally, a multi-component system may yield either a eutectic, salt, and/or a cocrystal. This study adopted a methodical orthogonal framework to analyze the final solid form. A single crystal X-ray structural investigation revealed the formation of a heterosynthon with carboxylic and benzimidazole groups of FEB and TEL, respectively, in the triclinic P-1 space group. ΔpKa of the heterosynthon is â¼1.5, hence, based on the empirical rules, a salt-cocrystal continuum is hypothesized. Further, attenuated total reflectance Fourier transform infrared (ATR-FTIR), and Raman spectroscopy were employed to corroborate the hydrogen bond formation in the heterosynthon (-N---H-O-), which confirmed the propensity for cocrystal formation. An accelerated stability study and an in vitro biorelevant dissolution study of the cocrystal were performed, which demonstrated that it is physiochemically stable, but it resulted in a slower dissolution rate when compared with plain drugs.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Gota
/
Hipertensão
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article