Combined eutexia and amorphization for simultaneous enhancement of dissolution rate of triamterene and hydrochlorothiazide: preparation of orodispersible tablets

Abstract

Background

Triamterene is an oral antihypertensive drug with dissolution-limited poor bioavailability. It can be used as monotherapy or in fixed dose combination with hydrochlorothiazide which also suffers from poor dissolution. Moreover, co-processing of drugs in fixed dose combination can alter their properties. Accordingly, pre-formulation studies should investigate the effect of co-processing and optimize the dissolution of drugs before and after fixed dose combination. This is expected to avoid deleterious interaction (if any) and to hasten the biopharmaceutical properties.

Objective

Accordingly, the aim of this work was to optimize the dissolution rate of triamterene alone and after fixed dose combination with hydrochlorothiazide.

Methodology

Triamterene was subjected to dry co-grinding with xylitol, HPMC-E5 or their combination. The effect of co-grinding with hydrochlorothiazide was also tested in absence and presence of xylitol and HPMC-E5. The products were assessed using Fourier-transform infrared (FTIR), differential scanning calorimetry, X-ray powder diffraction (XRPD), in addition to dissolution studies. Optimum formulations were fabricated as oral disintegrating tablets (ODT).Results: Co-processing of triamterene with xylitol formed eutectic system which hastened dissolution rate. HPMC-E5 resulted in partial amorphization and improved triamterene dissolution. Co-grinding with both materials combined their effects. Co-processing of triamterene with hydrochlorothiazide resulted in eutexia but the product was slowly dissolving due to aggregation. This problem was vanished in presence of HPMC-E5 and xylitol. Compression of the optimum formulation into ODT underwent fast disintegration and liberated acceptable amounts of both drugs.

Conclusion

The study introduced simple co-processing with traditional excipients for development of ODT of triamterene and hydrochlorothiazide.

Graphical Abstract

Keywords:

• Triamterene
• hydrochlorothiazide
• eutexia
• amorphization
• orodisintegrating

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

Hend A. Awad: investigation, data curation, visualization, and writing original draft. Mohamed I. Fetouh: conceptualization, methodology, supervision, and reviewing. Amal A. Sultan: conceptualization, methodology, visualization, supervision, writing, reviewing, and editing. Gamal M. El Maghraby: conceptualization, methodology, visualization, supervision, writing, reviewing, and editing.

Data availability statement

Data are available upon request from the corresponding author.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.