Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Using droplet-based microfluidic technology to study the precipitation of a poorly water-soluble weakly basic drug upon a pH-shift
AU - Edwards, Francine
AU - Tsakmaka, Christina
AU - Mohr, Stephan
AU - Fielden, Peter R.
AU - Goddard, Nick J.
AU - Booth, Jonathan
AU - Tam, Kin Y.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - NUCLEATION
KW - HUMANS
KW - DISSOLUTION
KW - SYSTEM
KW - FORMULATIONS
KW - SOLUBILITY
KW - SOLID DISPERSIONS
KW - ABSORPTION
U2 - 10.1039/c2an36364j
DO - 10.1039/c2an36364j
M3 - Journal article
VL - 138
SP - 339
EP - 345
JO - Analyst
JF - Analyst
SN - 0003-2654
IS - 1
ER -