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• W1998154319 endingPage "229" @default.
• W1998154319 startingPage "221" @default.
• W1998154319 abstract "Supersaturatable cosolvent (S-cosolvent) and supersaturatable self-emulsifying drug delivery systems (S-SEDDS) are designed to incorporate water soluble cellulosic polymers such as hydroxypropyl methylcellulose (HPMC), which may inhibit or retard drug precipitation in vivo. A poorly soluble drug, PNU-91325, was used as a model drug in this study to illustrate this formulation approach. The comparative in vitro studies indicated that the presence of a small amount HPMC in the formulation was critical to achieve a stabilized supersaturated state of PNU-91325 upon mixing with water. An in vivo study was conducted in dogs for assessment of the oral bioavailability of four formulations of PNU-91325. A five-fold higher bioavailability (approximately 60%) was observed from a S-cosolvent formulation containing propylene glycol (PG)+20 mg/g HPMC as compared to that (approximately 12%) of a neat polyethylene glycol (PEG) 400 formulation. The low bioavailability of the PEG 400 formulation is attributed to the uncontrolled precipitation of PNU-91325 upon dosing, a commonly observed phenomenon with the cosolvent approach. A S-SEDDS formulation composed of 30% w/w Cremophor (surfactant), 9% PEG 400, 5% DMA, 18% Pluronic L44, 20% HPMC, and other minor components showed an oral bioavailability of approximately 76%, comparable to that of a neat tween formulation (bioavailability: approximately 68%). The significant improvement of the oral bioavailability of the supersaturatable S-cosolvent and S-SEDDS formulations is attributed to a high free drug concentration in vivo as a result of the generation and stabilization of the supersaturated state due to the incorporation of polymeric precipitation inhibitor." @default.
• W1998154319 created "2016-06-24" @default.
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• W1998154319 date "2004-01-01" @default.
• W1998154319 modified "2023-10-16" @default.
• W1998154319 title "Enhanced Oral Bioavailability of a Poorly Water Soluble Drug PNU‐91325 by Supersaturatable Formulations" @default.
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• W1998154319 doi "https://doi.org/10.1081/ddc-120028718" @default.
• W1998154319 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/15089057" @default.
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