TY - JOUR

T1 - Development of a Microgram Scale Video-Microscopic Method to Investigate Dissolution Behavior of Poorly Water-Soluble Drugs

AU - Senniksen, Malte Bøgh

AU - Christfort, Juliane Fjelrad

AU - Marabini, Riccardo

AU - Spillum, Erik

AU - Matthews, Wayne

AU - Da Vià, Luigi

AU - Plum, Jakob

AU - Rades, Thomas

AU - Müllertz, Anette

N1 - Funding Information: M.B.S’s research stay was sponsored by BioSense Solutions ApS. JP was partly funded by the Innovation Fund Denmark (IFD) under File No. 8054-00056B.

PY - 2022

Y1 - 2022

N2 - Poor aqueous solubility is a common characteristic of new drug candidates, which leads to low or inconsistent oral bioavailability. This has sparked an interest in material efficient testing of solubility and dissolution rate. The aim was to develop a microgram scale video-microscopic method to screen the dissolution rates of poorly water-soluble drugs. This method was applied to six drugs (carvedilol, diazepam, dipyridamole, felodipine, fenofibrate, and indomethacin) in fasted state simulated intestinal fluid (FaSSIF), of indomethacin in buffer with varying pH, and of diazepam and dipyridamole in customized media. An additional aim was to track phase transformations for carbamazepine in FaSSIF. The dissolution rates and particle behavior of the drugs were investigated by tracking particle surface area over time using optical video-microscopy. Applying miniaturized UV spectroscopic dissolution resulted in a similar grouping of dissolution rates and pH effects, as for the video-microscopic setup. Using customized media showed that lysophospholipid enhanced the dissolution rate of diazepam and dipyridamole. The video-microscopic setup allowed for the nucleation of transparent particles on dissolving carbamazepine particles to be tracked over time. The developed setup offers a material efficient screening approach to group drugs according to dissolution rate, where the use of optical microscopy helps to achieve a high sample throughput. Graphical Abstract: [Figure not available: see fulltext.].

AB - Poor aqueous solubility is a common characteristic of new drug candidates, which leads to low or inconsistent oral bioavailability. This has sparked an interest in material efficient testing of solubility and dissolution rate. The aim was to develop a microgram scale video-microscopic method to screen the dissolution rates of poorly water-soluble drugs. This method was applied to six drugs (carvedilol, diazepam, dipyridamole, felodipine, fenofibrate, and indomethacin) in fasted state simulated intestinal fluid (FaSSIF), of indomethacin in buffer with varying pH, and of diazepam and dipyridamole in customized media. An additional aim was to track phase transformations for carbamazepine in FaSSIF. The dissolution rates and particle behavior of the drugs were investigated by tracking particle surface area over time using optical video-microscopy. Applying miniaturized UV spectroscopic dissolution resulted in a similar grouping of dissolution rates and pH effects, as for the video-microscopic setup. Using customized media showed that lysophospholipid enhanced the dissolution rate of diazepam and dipyridamole. The video-microscopic setup allowed for the nucleation of transparent particles on dissolving carbamazepine particles to be tracked over time. The developed setup offers a material efficient screening approach to group drugs according to dissolution rate, where the use of optical microscopy helps to achieve a high sample throughput. Graphical Abstract: [Figure not available: see fulltext.].

KW - bio-relevant dissolution

KW - dissolution rate

KW - poorly water-soluble drugs

KW - preformulation

KW - video-microscopy

U2 - 10.1208/s12249-022-02322-9

DO - 10.1208/s12249-022-02322-9

M3 - Journal article

C2 - 35739362

AN - SCOPUS:85132685646

VL - 23

JO - AAPS PharmSciTech

JF - AAPS PharmSciTech

SN - 1530-9932

IS - 6

M1 - 173

ER -