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- W1804105655 abstract "To preliminarily develop a surfactant-free, polymeric solid dispersion (PSD) of paclitaxel suitable for oral administration.A co-solvent quench method was applied to screen the proper polymer matrix of the PSD which were prepared in a liquid system using a quasi-emulsion solvent diffusion method (QESDM). Three dissolution experiments and two in vivo tests in rats were used to explain the differences among the formulations.The theoretical solubility ratio of amorphous/crystalline PTX was 92.6 (37 °C). Hydroxypropyl methylcellulose acetate succinate (HPMCAS) was chosen as the polymer carrier of the PSD and a porous silicon dioxide [called white carbon black (WCB)] was selectable to be used to further adjust the dissolution rate. The absolute oral bioavailability (AOB, 20 mg/kg) of the three formulas [HPMCAS/paclitaxel/WCB = 4/1/0 (F1), 8/1/0 (F2) and 4/1/4 (F3), w/w/w] were 11.8, 13.6 and 25.6%, respectively. The AOB of F3 is nearly seven times higher than that (3.8%) of paclitaxel material (a control). The advantage of higher HPMCAS/paclitaxel ratio of F2 in a dissolution test was not reflected in the first in vivo test due to the relatively higher dose of polymer which could not be effectively dissolved under the limitation of intestinal environment. This was deduced from the dissolution tests and was finally validated when the oral dose of PTX (and thus polymer) was reduced. The relevant AOBs (10 mg/kg) were 10.4, 20.8 and 19.6%, respectively.The PSD is a promising formulation strategy and the QESDM is a practical preparation method to implement such formulation design." @default.
- W1804105655 created "2016-06-24" @default.
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- W1804105655 date "2015-07-10" @default.
- W1804105655 modified "2023-10-18" @default.
- W1804105655 title "A pre-formulation study of a polymeric solid dispersion of paclitaxel prepared using a quasi-emulsion solvent diffusion method to improve the oral bioavailability in rats" @default.
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- W1804105655 doi "https://doi.org/10.3109/03639045.2015.1054398" @default.
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