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

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 (Na 2 CO 3 ). 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/Na 2 CO 3 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.

Comparison of Two Grafted Copolymers, Soluplus and Kollicoat IR, as Solid Dispersion Carriers of Arteether for Oral Delivery Prepared by Different Solvent-Based Methods

“…In solid dispersion, characteristic arteether peaks are either absent or present with significantly low intensity compared to that of the pure drug or its physical mixture. Reduction in peak intensities indicates loss of crystallinity . When a drug is dissolved in a solvent in the presence of a polymeric matrix, followed by solvent evaporation, it becomes dispersed in the polymeric matrix in either an amorphous or molecular dispersion form.…”

“…However, they have their drawbacks, such as the complexity of the SLN formulation or the high surfactant content of SEDDS. Solid dispersion is another popular approach to enhancing the dissolution of the poorly water-soluble drug. , For BCS class II drugs with dissolution rate-dependent oral absorption, the solid dispersion approach can significantly improve their oral bioavailability. , There are more than 30 US FDA-approved drug products based on the solid dispersion approach, and the number is increasing yearly . In amorphous solid dispersion (ASD), the active ingredient is dispersed in a substantially amorphous form within an excipient matrix.…”

“…10,11 For BCS class II drugs with dissolution rate-dependent oral absorption, the solid dispersion approach can significantly improve their oral bioavailability. 12,13 There are more than 30 US FDA-approved drug products based on the solid dispersion approach, and the number is increasing yearly. 14 In amorphous solid dispersion (ASD), the active ingredient is dispersed in a substantially amorphous form within an excipient matrix.…”

Development and Validation of HPLC Method for Determination of Benidipine Hydrochloride in Lipid Vesicles Formulations

“…The following equation was used to compute the drug entrapment efficiency: (4) For drug content, about 1 mL of transfersome, ethosome, and transethosome formulations equivalent to 1000 µg of BEN was properly diluted with methanol to reach a final concentration of 100 µg/ml. The HPLC technique was used to evaluate the drug content in samples using the following equation [21]:…”

Recent and Relevant Methodology in the Advancement of Solid Dispersion

“…The developed SD formulations resulted in a significant improvement in in vitro dissolution compared to pure drug. 62 K Wlodarski, developed tadalafil (Td) six different solid dispersions in the following polymers: HPMC, MC, PVP, PVP-VA, Kollicoat IR and Soluplus by freeze-drying. Apparent solubility and intrinsic dissolution rate studies revealed the greatest, a 16-fold, increase in drug solubility and a significant, 20-fold, dissolution rate enhancement for the Td/PVP-VA solid dispersion in comparison with crystalline Td.…”