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- W2489239983 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 IC 50 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." @default.
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- W2489239983 date "2016-07-29" @default.
- W2489239983 modified "2023-10-08" @default.
- W2489239983 title "Preformulation of FK506 Prodrugs for Improving Solubility" @default.
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- W2489239983 doi "https://doi.org/10.1002/bkcs.10861" @default.
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