Cocrystals of telmisartan: characterization, structure elucidation, in vivo and toxicity studies

Abstract

The present study reports novel cocrystals of telmisartan (TEL) with saccharin and glutaric acid. Crystal engineering approaches such as solution crystallization, solid-state grinding and slurry method have been utilized with the ultimate objective of improving the solubility of this BCS class II drug. The physical characterization revealed that the cocrystals are unique vis-à-vis thermal, spectroscopic and X-ray diffraction properties. Structural characterization showed that the cocrystals with saccharin and glutaric acid exist in monoclinic P2 1 /c and triclinic P1 space groups, respectively. The improved solubility of telmisartansaccharin (TEL-SAC) (nine-fold) and telmisartan-glutaric acid (two-fold) cocrystals in comparison with the free drug has been demonstrated in solubility experiments in phosphate buffer, pH 7.5. The TEL-SAC cocrystal remained stable in the aqueous medium for 6 hours as confirmed by PXRD. The AUC 0-24 of TEL-SAC and TEL-GA was found to be 2-fold and 1.4-fold increased in terms of bioavailability than pure TEL, respectively. The in vivo antihypertensive activity of TEL-SAC in DOCA salt-induced hypertensive rats showed two-fold improved efficacy, while acute toxicity studies revealed no signs of toxicity in rats even at doses of 2000 mg kg −1 of body weight (BW). The new solid phase of telmisartan with saccharin represents a promising and viable opportunity for the manufacture of a drug product with improved therapeutic outcomes.

Preparation and Characterization of Solid Dispersion Telmisartan – Hydroxypropyl Methyl Cellulose(HPMC) E5 LV by Co-Grinding Method

“…Therefore, it is necessary to improve the solubility and dissolution rate of TMS. Several studies have been conducted to improve the solubility and dissolution of TMS including co-grinding TMS with polyvinyl alcohol 3 , formation of solid nanoparticles 4 , inclusion complex of TMS and b-cyclodextrins 5 , formation of cocrystalline phase with several coformers 6,7 , formation amorphous solid dsipersion 8 .…”

Novel Pharmaceutical Cocrystal of Telmisartan and Hydrochlorothiazide

“…Previous studies, to improve the aqueous solubility of TEL, show the possibility of preparing solid dispersions [14][15][16], amorphous formulation [17], immediate release tablets [18], nanoparticles [19,20], and self-nanoemulsifying drug delivery systems [21,22]. However, the cocrystallization approach, for improving the aqueous solubility of TEL, has been investigated by Chadha et al [23] and by Alatas et al [24].…”

Cocristais: uma estratégia promissora na área farmacêutica

“…[63][64][65][73][74][75] O teor lipídico presente nos alimentos e a presença de sais biliares também podem melhorar o desempenho de um fármaco lipofílico/hidrofóbico in vivo. [111][112][113][114][115] No entanto, o efeito destes agentes de solubilização na solubilidade do cocristal geralmente não é tão simples.…”