title: Uniform nano-sized valsartan for dissolution and bioavailability enhancement: influence of particle size and crystalline state.
abstract: The central purpose of this study was to evaluate the impact of drug particle size and crystalline state on valsartan (VAL) formulations in order to improve its dissolution and bioavailability. VAL microsuspension (mean size 22 μm) and nanosuspension (30-80nm) were prepared by high speed dispersing and anti-solvent precipitation method and converted into powders through spray drying. Differential scanning calorimetry studies indicated amorphization of VAL in the spray-dried valsartan nanosuspension (SD-VAL-Nano) but recrystallization occurred after 6 months storage at room temperature. The spray-dried valsartan microsuspension (SD-VAL-Micro) conserved the crystalline form. The VAL dissolution rate and extent were markedly enhanced with both SD-VAL-Micro and SD-VAL-Nano as compared to crude VAL crystals over the pH range of 1.2-6.8. Pharmacokinetic studies in rats demonstrated a 2.5-fold increase in oral bioavailability in the case of SD-VAL-Nano compared with the commercial product while the SD-VAL-Micro provided a much less desirable pharmacokinetic profile. In conclusion, reducing particle size to the nano-scale appears to be a worthwhile and promising approach to obtain VAL products with optimum bioavailability. In addition, the impact of crystalline state on the bioavailability of nano-sized VAL might be not as big as that of particle size.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, PR China.
authors.forename: Qiuping
authors.initials: Q
authors.lastname: Ma
authors.forename: Hongrui
authors.initials: H
authors.lastname: Sun
authors.forename: Erxi
authors.initials: E
authors.lastname: Che
authors.forename: Xin
authors.initials: X
authors.lastname: Zheng
authors.forename: Tongying
authors.initials: T
authors.lastname: Jiang
authors.forename: Changshan
authors.initials: C
authors.lastname: Sun
authors.forename: Siling
authors.initials: S
authors.lastname: Wang
mesh_terms: D000284:Administration, Oral; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D004355:Drug Stability; D004356:Drug Storage; D006863:Hydrogen-Ion Concentration; D008297:Male; D008863:Microspheres; D053758:Nanoparticles; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013777:Tetrazoles / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D013997:Time Factors; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D000068756:Valsartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine