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- Title
Preformulation of FK506 Prodrugs for Improving Solubility.
- Authors
Na, Young-Guk; Jun, Hye-Suk; Kim, Daehee; Park, Byong-Chul; Lim, Si-Kyu; Lee, Ki-Ho; Hwang, Sung-Joo; Park, Jeong-Sook; Jung, Sang-Hun; Cho, Cheong-Weon
- Abstract
In order to improve water solubility of a lipophilic drug, tacrolimus ( FK506), two prodrugs ( FK506-G or FK506-S) such as FK506-M32-LS-G ( FK506-G) and FK506-M32-LS-SL ( FK506-S) were synthesized. Two prodrugs ( FK506-G or FK506-S), including FK506, were characterized by differential scanning calorimetry ( DSC), X-ray diffractometry ( XRD), scanning electron microscopy ( SEM), enzymatic kinetics, and cytotoxicity. A phase solubility test was conducted in distilled water, and the solubility of two prodrugs ( FK506-G or FK506-S) was measured in various pH values for pH solubility profiles. Most interesting was that FK506-S showed the highest solubility, 866 μg/ mL in water. In vitro enzymatic kinetics of two prodrugs ( FK506-G or FK506-S) in human plasma was evaluated by measuring the decrease of FK506-G or FK506-S as well as the increase of FK506 by HPLC, and FK506-G or FK506-S was metabolized in 1 h in human plasma. Two prodrugs ( FK506-G or FK506-S) including FK506 showed an IC50 of 336.6 μg/ mL for FK506, 337.9 μg/ mL for FK506-G, or 480.1 μg/ mL for FK506-S against a conjunctive cell line, Clone 1-5c-4 cells. Taken together, FK506-S could be the most optimal prodrug for aqueous preparations based on preformulation data.
- Subjects
TACROLIMUS; PRODRUGS; SOLUBILITY; DIFFERENTIAL scanning calorimetry; SCANNING electron microscopy; DISTILLED water
- Publication
Bulletin of the Korean Chemical Society, 2016, Vol 37, Issue 8, p1313
- ISSN
0253-2964
- Publication type
Article
- DOI
10.1002/bkcs.10861