Products Cited in Publications Worldwide Mechanochemical synthesis of telmisartan-based co-amorphous solid dispersions with enhanced solubility and unexpected cytotoxic synergy on normal cell lines

Mechanochemical synthesis of telmisartan-based co-amorphous solid dispersions with enhanced solubility and unexpected cytotoxic synergy on normal cell lines

Turek, Marika; Gach-Janczak, Katarzyna; Różycka-Sokołowska, Ewa; Owsianik, Krzysztof; Bałczewski, Piotr

DOI:

Abstract

Telmisartan (TEL), an angiotensin II receptor blocker (ARB), has poor bioavailability due to its low solubility. To improve dissolution profile and potential therapeutic efficacy of this drug, six TEL-based coamorphous solid dispersions (SDs) were synthesized using mechanochemical neat grinding with various active pharmaceutical ingredients (APIs): hydrochlorothiazide (HCT), amlodipine (AMLO), amlodipine besylate (AMLO-Bes), and rosuvastatin sodium (ROS-Na). The resulting binary and ternary SDs were characterized using X-ray powder diffraction (XRPD), Fourier-transform infrared spectroscopy (FT-IR), and differential scanning calorimetry (DSC). Stability tests confirmed that most SDs were stable for at least 12 months, except for the TEL/HCT system, which recrystallized after two months. Dissolution studies revealed 4–5 fold improvement in TEL release from co-amorphous SDs, especially in formulations with excipients. Cytotoxic activity was evaluated against cancerous (HepG2, MCF-7, HL-60) and normal (HUVEC and MCF-10A) cell lines. The studies revealed a clear synergistic cytotoxic effect of the TEL and ROS-Na combination, which is even more marked on normal cells.

Keywords

Bioavailability ; Cytotoxicity ; Mechanochemistry ; Solid dispersions ; Telmisartan ; Rosuvastatin ; Hydrochlorothiazide

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Amlodipine Besylate

A804204111470-99-697%

Amlodipine Besylate

11.0/1mg

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