title: Enhanced dissolution and oral bioavailability of valsartan solid dispersions prepared by a freeze-drying technique using hydrophilic polymers.
abstract: This study aimed to improve the dissolution rate and oral bioavailability of valsartan (VAL), a poorly soluble drug using solid dispersions (SDs). The SDs were prepared by a freeze-drying technique with polyethylene glycol 6000 (PEG6000) and hydroxypropylmethylcellulose (HPMC 100KV) as hydrophilic polymers, sodium hydroxide (NaOH) as an alkalizer, and poloxamer 188 as a surfactant without using any organic solvents. In vitro dissolution rate and physicochemical properties of the SDs were characterized using the USP paddle method, differential scanning calorimetry (DSC), X-ray diffractometry (XRD) and Fourier transform-infrared (FT-IR) spectroscopy, respectively. In addition, the oral bioavailability of SDs in rats was evaluated by using VAL (pure drug) as a reference. The dissolution rates of the SDs were significantly improved at pH 1.2 and pH 6.8 compared to those of the pure drug. The results from DSC, XRD showed that VAL was molecularly dispersed in the SDs as an amorphous form. The FT-IR results suggested that intermolecular hydrogen bonding had formed between VAL and its carriers. The SDs exhibited significantly higher values of AUC 0-24 h and Cmax in comparison with the pure drug. In conclusion, hydrophilic polymer-based SDs prepared by a freeze-drying technique can be a promising method to enhance dissolution rate and oral bioavailability of VAL.
authors.affiliation: a College of Pharmaceutical Sciences, Soochow University , Suzhou , People's Republic of China and.
authors.forename: Wei-Juan
authors.initials: WJ
authors.lastname: Xu
authors.affiliation: b Department of Pharmacy , Shanghai Changning Center Hospital , Shanghai , People's Republic of China.
authors.forename: Hong-Juan
authors.initials: HJ
authors.lastname: Xie
authors.affiliation: a College of Pharmaceutical Sciences, Soochow University , Suzhou , People's Republic of China and.
authors.forename: Qing-Ri
authors.initials: QR
authors.lastname: Cao
authors.affiliation: a College of Pharmaceutical Sciences, Soochow University , Suzhou , People's Republic of China and.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Shi
authors.affiliation: a College of Pharmaceutical Sciences, Soochow University , Suzhou , People's Republic of China and.
authors.forename: Yue
authors.initials: Y
authors.lastname: Cao
authors.affiliation: a College of Pharmaceutical Sciences, Soochow University , Suzhou , People's Republic of China and.
authors.forename: Xiao-Yin
authors.initials: XY
authors.lastname: Zhu
authors.affiliation: a College of Pharmaceutical Sciences, Soochow University , Suzhou , People's Republic of China and.
authors.forename: Jing-Hao
authors.initials: JH
authors.lastname: Cui
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000818:Animals; D001682:Biological Availability; D004337:Drug Carriers / Q000737:chemistry; D005612:Freeze Drying; D065347:Hypromellose Derivatives; D008297:Male; D020442:Poloxamer; D011092:Polyethylene Glycols; D011108:Polymers; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D000068756:Valsartan / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D004337:Drug Carriers; D011108:Polymers; D020442:Poloxamer; D065347:Hypromellose Derivatives; D011092:Polyethylene Glycols; D000068756:Valsartan
keywords: Dissolution rate; freeze-drying; oral bioavailability; solid dispersion; valsartan