title: Using droplet-based microfluidic technology to study the precipitation of a poorly water-soluble weakly basic drug upon a pH-shift.
abstract: The purpose of this study is to develop a droplet-based microfluidic device capable of monitoring drug precipitation upon a shift from gastric pH (pH 1.5) to intestinal pH (pH 6.5-7.0). The extent of precipitation occurring in droplets over time was measured using a novel on-chip laser scattering technique specifically developed for this study. The precipitation of ketoconazole, a poorly water-soluble basic drug, was investigated under different concentrations and pH values. It has been shown that the drug precipitates rapidly under supersaturation. Two water-soluble aqueous polymers, namely, polyvinylpyrrolidone (PVP) and hydroxypropylmethylcellulose (HPMC) have been evaluated as precipitation inhibitors. HPMC was shown to be the most potent precipitation inhibitor. It is envisaged that the microfluidic pH-shift method developed in this study would form a proof-of-concept study, towards the development of a high throughput method for screening pharmaceutical excipients/precipitation inhibitors.
authors.affiliation: School of Chemical Engineering and Analytical Science, The University of Manchester, PO Box 88, Sackville Street, Manchester M60 1QD, UK.
authors.forename: Francine
authors.initials: F
authors.lastname: Edwards
authors.forename: Christina
authors.initials: C
authors.lastname: Tsakmaka
authors.forename: Stephan
authors.initials: S
authors.lastname: Mohr
authors.forename: Peter R
authors.initials: PR
authors.lastname: Fielden
authors.forename: Nick J
authors.initials: NJ
authors.lastname: Goddard
authors.forename: Jonathan
authors.initials: J
authors.lastname: Booth
authors.forename: Kin Y
authors.initials: KY
authors.lastname: Tam
mesh_terms: D011232:Chemical Precipitation; D006863:Hydrogen-Ion Concentration; D007654:Ketoconazole / Q000737:chemistry*; D008027:Light; D046210:Microfluidic Analytical Techniques / Q000379:methods*; D012542:Scattering, Radiation; D012995:Solubility; D014867:Water / Q000737:chemistry*
chemical_list: D014867:Water; D007654:Ketoconazole