In:
Bulletin of the Korean Chemical Society, Wiley, Vol. 37, No. 8 ( 2016-08), p. 1313-1319
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.
Type of Medium:
Online Resource
ISSN:
1229-5949
,
1229-5949
DOI:
10.1002/bkcs.2016.37.issue-8
Language:
English
Publisher:
Wiley
Publication Date:
2016
detail.hit.zdb_id:
2056474-0
Permalink