title: Preparation and in vitro/in vivo evaluation of revaprazan hydrochloride nanosuspension.
abstract: Revaprazan hydrochloride (RH) is a new reversible proton pump inhibitor. However, due to poor water solubility, oral bioavailability of the drug was relatively low. To investigate the particle size reduction effect of RH on dissolution and absorption, three suspensions that containing different sized particles were prepared by high pressure homogenization and in vitro/in vivo evaluations were carried out. DSC and powder X-ray diffraction were used to study crystalline state of freeze dried powder of RH suspensions and the results showed that particles of RH microsuspension and nanosuspension remained in the same crystalline state as coarse suspension, but had lower lattice energy. In the in vitro dissolution test, both microsuspension and nanosuspension showed increased dissolution rate. In the in vivo evaluation, compared to coarse suspension, RH nanosuspension exhibited significant increase in AUC(0-t), C(max) and decrease in T(max), MRT. Nevertheless, RH microsuspension did not display any significant differences in these pharmacokinetic parameters compared to the coarse suspension. The findings revealed that particle size reduction can influence RH absorption in gastrointestinal tract and nanosuspension can enhance oral bioavailability of RH in rats.
authors.affiliation: Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103# Wenhua Road, Shenyang, Liaoning 110016, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Yang
authors.forename: Yongshou
authors.initials: Y
authors.lastname: Tian
authors.forename: Xinlan
authors.initials: X
authors.lastname: Xu
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.forename: Liwei
authors.initials: L
authors.lastname: Mu
authors.forename: Yaqiong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Liang
authors.initials: L
authors.lastname: Fang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry*; D005612:Freeze Drying; D008297:Male; D008855:Microscopy, Electron, Scanning; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D044367:Phase Transition; D011208:Powders; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D011744:Pyrimidinones / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013499:Surface Properties; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D014961:X-Ray Diffraction
chemical_list: D004337:Drug Carriers; D011208:Powders; D054328:Proton Pump Inhibitors; D011744:Pyrimidinones; D044005:Tetrahydroisoquinolines; C108798:YH 1885