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Lyophilized Amorphous Dispersion of Telmisartan in a Combined Carrier–Alkalizer System: Formulation Development and In Vivo Study
journal contribution
posted on 2020-12-10, 22:03 authored by Khater A. S. Al-Japairai, Hala M. Alkhalidi, Syed Mahmood, Samah H. Almurisi, Abd Almonem Doolaanea, Taha A. Al-Sindi, Bappaditya ChatterjeeTelmisartan suffers from low oral bioavailability
due to its poor water solubility. The research work presents a formulation
of solid dispersed (SD) telmisartan formulation as a ternary mixture
of a drug, a polymeric carrier (poly(vinylpyrrolidone) (PVP) K30),
and an alkalizer (Na2CO3). The preparation method,
which was lyophilization of an aqueous solution containing the ingredients,
was free from any organic solvent. The developed SD formulations resulted
in a significant improvement in in vitro dissolution
(>90% drug dissolution in 15 min) compared to pure telmisartan.
Solid-state characterization by scanning electron microscopy (SEM),
differential scanning calorimetry (DSC), and X-ray diffraction (XRD)
studies indicated the conversion of crystalline telmisartan into an
amorphous form. Fourier transform infrared (FTIR) spectroscopy revealed
the drug–polymer interaction that was responsible for reducing
the chances of recrystallization. A short-term stability study showed
that selected SD formulations were stable in terms of in vitro dissolution and retained their amorphous structure in ambient and
accelerated conditions over 2 months. Selected formulations (drug/PVP
K30/Na2CO3 as 1:1:2 or 1:2:2 weight ratio) resulted
in >2.48 times relative oral bioavailability compared to marketed
formulations. It was considered that the incorporation of an alkalizer
and a hydrophilic polymer, and amorphization of telmisartan by lyophilization,
could enhance in vitro dissolution and improve oral
bioavailability.