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

Autor:	Awad HA; Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Egyptian Russian University, Badr city, Egypt., Fetouh MI; Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Egyptian Russian University, Badr city, Egypt., Sultan AA; Department of Pharmaceutics, College of Pharmacy, University of Hafr Al-Batin, Hafr Al-Batin, Saudi Arabia.; Department of Pharmaceutical Technology, Faculty of Pharmacy, Tanta University, Tanta, Egypt., El Maghraby GM; Department of Pharmaceutical Technology, Faculty of Pharmacy, Tanta University, Tanta, Egypt.
Jazyk:	angličtina
Zdroj:	Drug development and industrial pharmacy [Drug Dev Ind Pharm] 2024 Apr; Vol. 50 (4), pp. 306-319. Date of Electronic Publication: 2024 Mar 06.
DOI:	10.1080/03639045.2024.2323996
Abstrakt:	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.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu