In-Vitro Characterization and Oral Bioavailability of Organic Solvent-free Solid Dispersions Containing Telmisartan

TY - JOUR

T1 - In-Vitro Characterization and Oral Bioavailability of Organic Solvent-free Solid Dispersions Containing Telmisartan

AU - Cao, Yue

AU - Shi, Li-Li

AU - Cao, Qing-Ri

AU - Yang, Mingshi

AU - Cui, Jing-Hao

PY - 2016/3/1

Y1 - 2016/3/1

N2 - Poorly water-soluble drugs often suffer from limited or irreproducible clinical response due to their low solubility and dissolution rate. In this study, organic solvent-free solid dispersions (OSF-SDs) containing telmisartan (TEL) were prepared using polyvinylpyrrolidone K30 (PVP K30) and polyethylene glycol 6000 (PEG 6000) as hydrophilic polymers, sodium hydroxide (NaOH) as an alkalizer, and poloxamer 188 as a surfactant by a lyophilization method. In-vitro dissolution rate and physicochemical properties of the OSF-SDs were characterized using the USP I basket method, differential scanning calorimetry (DSC), X-ray diffractometry (XRD) and fourier transform-infrared (FT-IR) spectroscopy. In addition, the oral bioavailability of OSF-SDs in rats was evaluated by using TEL bulk powder as a reference. The dissolution rates of the OSF-SDs were significantly enhanced as compared to TEL bulk powder. The results from DSC, XRD showed that TEL was molecularly dispersed in the OSF-SDs as an amorphous form. The FT-IR results suggested that intermolecular hydrogen bonding had formed between TEL and its carriers. The OSF-SDs exhibited significantly higher AUC0-24 h and Cmax, but similar Tmax as compared to the reference. This study demonstrated that OSF-SDs can be a promising method to enhance the dissolution rate and oral bioavailability of TEL.

AB - Poorly water-soluble drugs often suffer from limited or irreproducible clinical response due to their low solubility and dissolution rate. In this study, organic solvent-free solid dispersions (OSF-SDs) containing telmisartan (TEL) were prepared using polyvinylpyrrolidone K30 (PVP K30) and polyethylene glycol 6000 (PEG 6000) as hydrophilic polymers, sodium hydroxide (NaOH) as an alkalizer, and poloxamer 188 as a surfactant by a lyophilization method. In-vitro dissolution rate and physicochemical properties of the OSF-SDs were characterized using the USP I basket method, differential scanning calorimetry (DSC), X-ray diffractometry (XRD) and fourier transform-infrared (FT-IR) spectroscopy. In addition, the oral bioavailability of OSF-SDs in rats was evaluated by using TEL bulk powder as a reference. The dissolution rates of the OSF-SDs were significantly enhanced as compared to TEL bulk powder. The results from DSC, XRD showed that TEL was molecularly dispersed in the OSF-SDs as an amorphous form. The FT-IR results suggested that intermolecular hydrogen bonding had formed between TEL and its carriers. The OSF-SDs exhibited significantly higher AUC0-24 h and Cmax, but similar Tmax as compared to the reference. This study demonstrated that OSF-SDs can be a promising method to enhance the dissolution rate and oral bioavailability of TEL.

KW - Journal Article

M3 - Journal article

C2 - 27642309

SN - 1726-6882

VL - 15

SP - 385

EP - 394

JO - Iranian Journal of Pharmaceutical Research

JF - Iranian Journal of Pharmaceutical Research

IS - 2

ER -