| Autor: |
Zhang W; Magee Womens Research Institute, University of Pittsburgh , Pittsburgh, PA , USA ., Parniak MA, Mitsuya H, Sarafianos SG, Graebing PW, Rohan LC |
| Jazyk: |
angličtina |
| Zdroj: |
Drug development and industrial pharmacy [Drug Dev Ind Pharm] 2014 Aug; Vol. 40 (8), pp. 1101-11. Date of Electronic Publication: 2013 Jul 10. |
| DOI: |
10.3109/03639045.2013.809535 |
| Abstrakt: |
4'-Ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) is a novel nucleoside analog of great interest because of its superior activity against wild-type and multidrug-resistant HIV-1 strains, and favorable safety profiles in vitro and in vivo. The aim of this work was to provide preformulation information of EFdA important for delivery system development. A simple, accurate and specific reverse-phase high performance liquid chromatographic (RP-HPLC) method with UV detection was developed for quantification of EFdA. In addition, physicochemical characterizations including pH solubility profile, octanol/water partition coefficient (Log Po/w), DSC analysis, field emission scanning electron microscopy, and stability studies under various conditions were conducted. EFdA existed in planar or flake shape, with a melting point of ∼130 °C, and had a pH dependent solubility. The log Po/w value of EFdA was -1.19. The compound was stable upon exposure to pH levels from 3 to 9 and showed good stability at elevated temperature (65 °C). In vitro cytotoxicity assessments were performed in two different epithelial cell lines. In cell-based studies, the EFdA selectivity index (50% cytotoxic concentration [CC50] values/50% effective concentration [EC50]) was found to be greater than 1 × 10(3). Permeability studies using cell- and tissue-based models showed that EFdA had an apparent permeability coefficient (Papp) <1 × 10(-6)cm/s and that the paracelluar pathway was the dominant transport route for EFdA. Overall, EFdA possesses favorable characteristics for further formulation development. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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