title: In vitro/in vivo evaluation of felodipine micropowders prepared by the wet-milling process combined with different solidification methods.
abstract: In order to improve the in vitro dissolution rate and in vivo oral bioavailability of the poorly water soluble drug, felodipine (FELO), the wet-milling process was employed involving co-grinding with HPMC E5 and the in vitro release rate as investigated. After solidification by spray drying or freeze drying, the microsized powders were characterized in terms of their size, morphology, and in vitro dissolution rate. The oral bioavailability of this dry powder for suspension was evaluated in rats. After milling with 8% HPMC E5 and freeze drying, the powder mixture had an average particle size of 2.249 ± 1.497 μm and displayed an excellent dissolution rate of up to 93.2% within 10 minutes. DSC and PXRD investigations confirmed the absence of any crystal transformation during the wet-milling process. Using two different solidification methods, powders were stable for 6 months with regard to their in vitro dissolution rate. Significantly improved bioavailability was obtained for the wet-milled suspension before solidification and freeze dried powders with 6.8- (p < 0.001) and 3.6-fold (p < 0.01) increases, respectively, compared with that of the un-milled FELO. Also, no marked difference (p > 0.05) in bioavailability was seen for the spray dried powders. These effects suggest that the solidification method plays an important role in modifying the bioavailability of FELO after wet milling. Consequently, wet-milling is an effective technique to enhance the bioavailability of FELO and to maintain these benefits, freeze-drying is a feasible approach to solidifying the wet-milled suspension for industrial applications.
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University , Shenyang , PR China.
authors.forename: Jia
authors.initials: J
authors.lastname: Meng
authors.forename: Song
authors.initials: S
authors.lastname: Li
authors.forename: Qing
authors.initials: Q
authors.lastname: Yao
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Weng
authors.forename: Cuifang
authors.initials: C
authors.lastname: Cai
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.forename: Xing
authors.initials: X
authors.lastname: Tang
mesh_terms: D000818:Animals; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D002152:Calorimetry, Differential Scanning; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods*; D065546:Drug Liberation; D015736:Felodipine / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D065347:Hypromellose Derivatives / Q000737:chemistry*; D008297:Male; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D044367:Phase Transition; D011208:Powders; D051381:Rats; D012995:Solubility; D013499:Surface Properties; D014961:X-Ray Diffraction
chemical_list: D002121:Calcium Channel Blockers; D004337:Drug Carriers; D011208:Powders; D065347:Hypromellose Derivatives; D015736:Felodipine
keywords: Bioavailability; dissolution; felodipine; solidification; stability; wet-milling