Using droplet-based microfluidic technology to study the precipitation of a poorly water-soluble weakly basic drug upon a pH-shift

Francine Edwards; Christina Tsakmaka; Stephan Mohr; Peter R Fielden; Nick J Goddard; Jonathan Booth; Kin Y Tam

doi:10.1039/c2an36364j

Using droplet-based microfluidic technology to study the precipitation of a poorly water-soluble weakly basic drug upon a pH-shift

Francine Edwards, Christina Tsakmaka, Stephan Mohr, Peter R Fielden, Nick J Goddard, Jonathan Booth, Kin Y Tam

Research output: Contribution to journal › Article › peer-review

Abstract

The purpose of this study is to develop a droplet-based microfluidic device capable of monitoring drug pptn. upon a shift from gastric pH (pH 1.5) to intestinal pH (pH 6.5-7.0). The extent of pptn. occurring in droplets over time was measured using a novel on-chip laser scattering technique specifically developed for this study. The pptn. of ketoconazole, a poorly water-sol. basic drug, was investigated under different concns. and pH values. It has been shown that the drug ppts. rapidly under supersatn. Two water-sol. aq. polymers, namely, polyvinylpyrrolidone (PVP) and hydroxypropylmethylcellulose (HPMC) have been evaluated as pptn. inhibitors. HPMC was shown to be the most potent pptn. 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/pptn. inhibitors. [on SciFinder(R)]

Original language	English
Pages (from-to)	339-345
Number of pages	7
Journal	Analyst (Cambridge, U. K.)
Volume	138
Issue number	1
DOIs	https://doi.org/10.1039/c2an36364j
Publication status	Published - 2013

Keywords

Digestive tract
High throughput screening
Lab-on-a-chip
Microfluidic devices
Pharmaceutical excipients
Precipitation
Solubility
Stabilizing agents
Supersaturation
pH (using droplet-based microfluidic technol. to study the pptn. of a poorly water-sol. weakly basic drug upon a pH-shift)
droplet microfluidic pptn supersatn ketoconazole soly pH stomach intestine

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10.1039/c2an36364j

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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 pptn. upon a shift from gastric pH (pH 1.5) to intestinal pH (pH 6.5-7.0). The extent of pptn. occurring in droplets over time was measured using a novel on-chip laser scattering technique specifically developed for this study. The pptn. of ketoconazole, a poorly water-sol. basic drug, was investigated under different concns. and pH values. It has been shown that the drug ppts. rapidly under supersatn. Two water-sol. aq. polymers, namely, polyvinylpyrrolidone (PVP) and hydroxypropylmethylcellulose (HPMC) have been evaluated as pptn. inhibitors. HPMC was shown to be the most potent pptn. 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/pptn. inhibitors. [on SciFinder(R)]",

keywords = "Digestive tract, High throughput screening, Lab-on-a-chip, Microfluidic devices, Pharmaceutical excipients, Precipitation, Solubility, Stabilizing agents, Supersaturation, pH (using droplet-based microfluidic technol. to study the pptn. of a poorly water-sol. weakly basic drug upon a pH-shift), droplet microfluidic pptn supersatn ketoconazole soly pH stomach intestine",

author = "Francine Edwards and Christina Tsakmaka and Stephan Mohr and Fielden, {Peter R} and Goddard, {Nick J} and Jonathan Booth and Tam, {Kin Y}",

note = "CAN 158:21465 Pharmaceuticals 9003-39-8 (Polyvinylpyrrolidone); 9004-65-3 (Hydroxypropylmethylcellulose) Role: MOA (Modifier or additive use), USES (Uses) (solubilizer; using droplet-based microfluidic technol. to study the pptn. of a poorly water-sol. weakly basic drug upon a pH-shift); 65277-42-1 (Ketoconazole) Role: PEP (Physical, engineering or chemical process), PRP (Properties), THU (Therapeutic use), BIOL (Biological study), PROC (Process), USES (Uses) (using droplet-based microfluidic technol. to study the pptn. of a poorly water-sol. weakly basic drug upon a pH-shift)",

year = "2013",

doi = "10.1039/c2an36364j",

language = "English",

volume = "138",

pages = "339--345",

journal = "Analyst (Cambridge, U. K.)",

issn = "0003-2654",

publisher = "Royal Society of Chemistry",

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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

N1 - CAN 158:21465 Pharmaceuticals 9003-39-8 (Polyvinylpyrrolidone); 9004-65-3 (Hydroxypropylmethylcellulose) Role: MOA (Modifier or additive use), USES (Uses) (solubilizer; using droplet-based microfluidic technol. to study the pptn. of a poorly water-sol. weakly basic drug upon a pH-shift); 65277-42-1 (Ketoconazole) Role: PEP (Physical, engineering or chemical process), PRP (Properties), THU (Therapeutic use), BIOL (Biological study), PROC (Process), USES (Uses) (using droplet-based microfluidic technol. to study the pptn. of a poorly water-sol. weakly basic drug upon a pH-shift)

PY - 2013

Y1 - 2013

N2 - The purpose of this study is to develop a droplet-based microfluidic device capable of monitoring drug pptn. upon a shift from gastric pH (pH 1.5) to intestinal pH (pH 6.5-7.0). The extent of pptn. occurring in droplets over time was measured using a novel on-chip laser scattering technique specifically developed for this study. The pptn. of ketoconazole, a poorly water-sol. basic drug, was investigated under different concns. and pH values. It has been shown that the drug ppts. rapidly under supersatn. Two water-sol. aq. polymers, namely, polyvinylpyrrolidone (PVP) and hydroxypropylmethylcellulose (HPMC) have been evaluated as pptn. inhibitors. HPMC was shown to be the most potent pptn. 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/pptn. inhibitors. [on SciFinder(R)]

AB - The purpose of this study is to develop a droplet-based microfluidic device capable of monitoring drug pptn. upon a shift from gastric pH (pH 1.5) to intestinal pH (pH 6.5-7.0). The extent of pptn. occurring in droplets over time was measured using a novel on-chip laser scattering technique specifically developed for this study. The pptn. of ketoconazole, a poorly water-sol. basic drug, was investigated under different concns. and pH values. It has been shown that the drug ppts. rapidly under supersatn. Two water-sol. aq. polymers, namely, polyvinylpyrrolidone (PVP) and hydroxypropylmethylcellulose (HPMC) have been evaluated as pptn. inhibitors. HPMC was shown to be the most potent pptn. 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/pptn. inhibitors. [on SciFinder(R)]

KW - Digestive tract

KW - High throughput screening

KW - Lab-on-a-chip

KW - Microfluidic devices

KW - Pharmaceutical excipients

KW - Precipitation

KW - Solubility

KW - Stabilizing agents

KW - Supersaturation

KW - pH (using droplet-based microfluidic technol. to study the pptn. of a poorly water-sol. weakly basic drug upon a pH-shift)

KW - droplet microfluidic pptn supersatn ketoconazole soly pH stomach intestine

U2 - 10.1039/c2an36364j

DO - 10.1039/c2an36364j

M3 - Article

SN - 0003-2654

VL - 138

SP - 339

EP - 345

JO - Analyst (Cambridge, U. K.)

JF - Analyst (Cambridge, U. K.)

IS - 1

ER -

Using droplet-based microfluidic technology to study the precipitation of a poorly water-soluble weakly basic drug upon a pH-shift

Abstract

Keywords

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