20.500.12556/RUL-141963 Proof-of-concept for a miniaturized shake-flask biopharmaceutical solubility determination by sonic mixing The solvent volume must be very small to obtain biopharmaceutically relevant drug solubility data with low consumption of the solid sample which is often in low supply during early drug development. However, the adequate and repeatable mixing of a small volume can be challenging. We therefore developed a straightforward technique based on the shake-flask method which employed only sonication for mixing a very small amount of drug in an aqueous solvent at a stable pH and temperature. To test the technique, the solubilities of the model compounds carvedilol, digoxin, propranolol, theophylline, and verapamil were determined. The determined solubility values agreed well with the conventional shake-flask solubility data obtained in our laboratory and previously published literature data. The time necessary for the measurements (24 h), was shown to be similar to the conventional shake-flask method even for the low solubility drugs digoxin and carvedilol. The solubility % pH dependence can be established very well as shown with verapamil and propranolol and confirmed with a pH in-dependent solubility of theophylline. pharmacokinetics physiologically based pharmacokinetic (PBPK) modeling gastro plus modeling clinical trial simulation(s) bioequivalence biopharmaceutics classification system (BCS) virtual bioequivalence (VBE) biofarmacija farmakokinetika modeliraje simulacije kliničnih poskusov bioekvivalenca true false true Angleški jezik Slovenski jezik Članek v reviji 2022-10-13 08:16:25 2022-10-13 08:16:30 2022-10-14 03:58:05 0000-00-00 00:00:00 2020 0 0 Str. 626-631 no. 12 Vol. 75 2020 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 544.351.3:615 0031-7144 10.1691/ph.2020.0063 40934147 s2_(1).pdf s2_(1).pdf 1 D01F23B96110D3FCAD3828AEAE29EB59 5d24fa214f5f51dc8cdf8508dbf4d8506a02d34315cce751f60ae6c0d32295a3 d78a7c2d-4abe-11ed-9c94-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=163188 https://www.ingentaconnect.com/content/govi/pharmaz/2020/00000075/00000012/art00002;jsessionid=8dusoaec85aq3.x-ic-live-01 Dostop z geslom 1 89e753b1-4abe-11ed-9c94-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=163187 Fakulteta za farmacijo 0 0 0