Abstract
GLM-7 is a novel anti-leukemia drug in the pre-clinical study. The previous study shows that GLM-7 is a poorly water-soluble drug with low oral bioavailability. In this study, we employed the self-emulsifying drug delivery system (SEDDS) to improve the oral bioavailability of GLM-7. The GLM-7 SEDDS formulation was prepared using MCT as oil, ovolecithin as surfactant and Transcutol as co-surfactant, and the formulation parameters were optimized by the response surface methodology. The optimized GLM-7 SEDDS formulation showed a stable liquid state, and can automatically emulsify to form the isotropic emulsion once exposure to the water phase. The generated emulsion showed the spherical shape, and had an average size of about 399nm and a zeta potential of about -42mV. Compared to the GLM-7 dissolution less than 1.4% from pure GLM-7 powder (reference), the GLM-7 SEDDS formulation could remarkably enhance the in vitro dissolution to 83% in the medium of 0.1N HCL. The in vivo oral bioavailability of GLM-7 SEDDS formulation was investigated in beagle dogs. The results demonstrated that the GLM-7 SEDDS formulation significantly enhanced the plasma concentrations of GLM-7, and the Cmax reached to 878ng/ml and was 9.2 folds as high as the Cmax 95.85ng/ml of reference. Moreover, the area under the curve (AUC) of GLM-7 SEDDS formulation was 13.6 times higher than that of reference, which suggested that the SEDDS formulation remarkably increased the oral bioavailability of GLM-7.
Keywords: Bioavailability, dissolution, oral drug delivery, poorly water-soluble drugs, self-emulsifying drug delivery system.
Graphical Abstract
Current Drug Delivery
Title:Enhancing in vivo Bioavailability in Beagle Dogs of GLM-7 as a Novel Anti-Leukemia Drug through a Self-Emulsifying Drug Delivery System for Oral Delivery
Volume: 13 Issue: 1
Author(s): Yuli Wang, Ning Yu, Rui Guo, Meiyan Yang, Li Shan, Wei Huang, Wei Gong, Shuai Shao, Xiaoping Chen and Chunsheng Gao
Affiliation:
Keywords: Bioavailability, dissolution, oral drug delivery, poorly water-soluble drugs, self-emulsifying drug delivery system.
Abstract: GLM-7 is a novel anti-leukemia drug in the pre-clinical study. The previous study shows that GLM-7 is a poorly water-soluble drug with low oral bioavailability. In this study, we employed the self-emulsifying drug delivery system (SEDDS) to improve the oral bioavailability of GLM-7. The GLM-7 SEDDS formulation was prepared using MCT as oil, ovolecithin as surfactant and Transcutol as co-surfactant, and the formulation parameters were optimized by the response surface methodology. The optimized GLM-7 SEDDS formulation showed a stable liquid state, and can automatically emulsify to form the isotropic emulsion once exposure to the water phase. The generated emulsion showed the spherical shape, and had an average size of about 399nm and a zeta potential of about -42mV. Compared to the GLM-7 dissolution less than 1.4% from pure GLM-7 powder (reference), the GLM-7 SEDDS formulation could remarkably enhance the in vitro dissolution to 83% in the medium of 0.1N HCL. The in vivo oral bioavailability of GLM-7 SEDDS formulation was investigated in beagle dogs. The results demonstrated that the GLM-7 SEDDS formulation significantly enhanced the plasma concentrations of GLM-7, and the Cmax reached to 878ng/ml and was 9.2 folds as high as the Cmax 95.85ng/ml of reference. Moreover, the area under the curve (AUC) of GLM-7 SEDDS formulation was 13.6 times higher than that of reference, which suggested that the SEDDS formulation remarkably increased the oral bioavailability of GLM-7.
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Wang Yuli, Yu Ning, Guo Rui, Yang Meiyan, Shan Li, Huang Wei, Gong Wei, Shao Shuai, Chen Xiaoping and Gao Chunsheng, Enhancing in vivo Bioavailability in Beagle Dogs of GLM-7 as a Novel Anti-Leukemia Drug through a Self-Emulsifying Drug Delivery System for Oral Delivery, Current Drug Delivery 2016; 13 (1) . https://dx.doi.org/10.2174/1570159X13666150713173838
DOI https://dx.doi.org/10.2174/1570159X13666150713173838 |
Print ISSN 1567-2018 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5704 |
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