Effects of crystalline state and self-nanoemulsifying drug delivery system (SNEDDS) on oral bioavailability of the novel anti-HIV compound 6-benzyl-1-benzyloxymethyl-5-iodouracil in rats |
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| Authors: | Ying-Yuan Lu Wen-Bing Dai Xin Wang Xiao-Wei Wang Jun-Yi Liu Pu Li |
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| Affiliation: | 1. Department of Pharmacology, School of Basic Medical Science, Beijing (Peking) University, Beijing, PR China;2. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Beijing (Peking) University, Beijing, PR China;3. Department of Chemical Biology, School of Pharmaceutical Sciences, Beijing (Peking) University, Beijing, PR China |
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| Abstract: | The objective of this study was to investigate the effect of crystalline state and a formulation of self-nanoemulsifying drug delivery system (SNEDDS) on oral bioavailability of 6-benzyl-1-benzyloxymethyl-5-iodouracil (W-1), a novel non-nucleoside reverse transcriptase inhibitor, in rats. The crystalline states of W-1 were characterized by scanning electron microscope (SEM), differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD). The SNEDDS was formulated by medium-chain lipids, characterized by droplet particle size. The plasma concentrations of W-1 were measured by high performance liquid chromatography (HPLC). The results indicated that W-1 compound were presented as crystalline forms, A and B, the degree of crystallization in form B was higher than that in form A. The SNEDDS of W-1 displayed a significant increase in the dissolution rate than W-1 powder. Furthermore, after oral administration of W-1 (100?mg/kg), the pharmacokinetic parameters of form A, form B, and W-1 SNEDDS were as follows: AUC0-t 526.4?±?123.5, 305.1?±?58.5 and 2297?±?451?ng h/mL (p?
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| Keywords: | 6-Benzyl-1-benzyloxymethyl-5-iodouracil (W-1) crystalline state self-nanoemulsifying drug delivery system (SNEDDS) oral bioavailability rat |
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