Lyophilized Amorphous Dispersion of Telmisartan in a Combined Carrier-Alkalizer System: Formulation Development and In Vivo Study

Khater A S Al-Japairai; Hala M Alkhalidi; Syed Mahmood; Samah H Almurisi; Abd Almonem Doolaanea; Taha A Al-Sindi; Bappaditya Chatterjee

doi:10.1021/acsomega.0c04588

Lyophilized Amorphous Dispersion of Telmisartan in a Combined Carrier-Alkalizer System: Formulation Development and In Vivo Study

ACS Omega. 2020 Dec 10;5(50):32466-32480. doi: 10.1021/acsomega.0c04588. eCollection 2020 Dec 22.

Authors

Khater A S Al-Japairai^{1

2}, Hala M Alkhalidi³, Syed Mahmood¹, Samah H Almurisi², Abd Almonem Doolaanea², Taha A Al-Sindi⁴, Bappaditya Chatterjee^{2

5}

Affiliations

¹ Department of Pharmaceutical Engineering, Faculty of Chemical and Process Engineering Technology, University Malaysia Pahang, Gambang 26300, Malaysia.
² Department of Pharmaceutical Technology, Kulliyyah of Pharmacy, International Islamic University Malaysia (IIUM), Kuantan 25200, Malaysia.
³ Department of Clinical Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21441, Saudi Arabia.
⁴ Department of Basic Medical Science, Kulliyyah of Medicine, International Islamic University Malaysia (IIUM), Kuantan 25200, Malaysia.
⁵ SPP School of Pharmacy & Technology Management, SVKM's NMIMS, Vile Parle (East), Mumbai 400056, India.

Abstract

Telmisartan 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.