In vitro/in vivo evaluation of felodipine micropowders prepared by the wet-milling process combined with different solidification methods. (July 2014)

• Record Type: Journal Article
• Authors: Meng, Jia; Li, Song; Yao, Qing; Zhang, Ling; Weng, Yan; Cai, Cuifang; Xu, Hui; Tang, Xing
• Is Part Of: Drug development and industrial pharmacy. Volume 40:Number 7(2014:Jul.)
• Page Start: 929
• Page End: 936
• Publication Date: 2014-07
• Subjects: Pharmaceutical chemistry -- Periodicals; Pharmaceutical industry -- Periodicals; Drug Industry -- Periodicals; Technology, Pharmaceutical -- Periodicals; 615.05
• DOI: 10.3109/03639045.2013.790409
• Languages: English
• ISSNs: 0363-9045

Abstract

<abstract> <title>Abstract</title> <p>In order to improve the <italic><italic>in vitro</italic></italic> dissolution rate and <italic><italic>in vivo</italic></italic> oral bioavailability of the poorly water soluble drug, felodipine (FELO), the wet-milling process was employed involving co-grinding with HPMC E5 and the <italic>in vitro</italic> release rate as investigated. After solidification by spray drying or freeze drying, the microsized powders were characterized in terms of their size, morphology, and <italic>in vitro</italic> 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 <italic>in vitro</italic> dissolution rate. Significantly improved bioavailability was obtained for the wet-milled suspension before solidification and freeze dried powders with 6.8- (<italic>p</italic> < 0.001) and 3.6-fold (<italic>p</italic> < 0.01) increases, respectively, compared with that of the un-milled FELO. Also, no marked difference (<italic>p</italic> > 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.</p> </abstract>