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Preparation, characterization, and in vivo evaluation of a self-nanoemulsifying drug delivery system (SNEDDS) loaded with morin-phospholipid complex

Authors Zhang J, Peng Q, Shi S, Zhang Q, Sun X, Gong T, Zhang Z

Published 19 December 2011 Volume 2011:6 Pages 3405—3414

DOI https://doi.org/10.2147/IJN.S25824

Review by Single-blind

Peer reviewer comments 3

Jinjie Zhang1, Qiang Peng1, Sanjun Shi1, Qiang Zhang2, Xun Sun1, Tao Gong1, Zhirong Zhang1
1Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, People's Republic of China; 2State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Peking, People's Republic of China

Background: As a poorly water-soluble drug, the oral application of morin is limited by its low oral bioavailability. In this study, a new self-nanoemulsifying drug delivery system (SNEDDS), based on the phospholipid complex technique, was developed to improve the oral bioavailability of morin.
Methods: Morin-phospholipid complex (MPC) was prepared by a solvent evaporation method and characterized by infrared spectroscopy and X-ray diffraction. After formation of MPC, it was found that the liposolubility of morin was significantly increased, as verified through solubility studies. An orthogonal design was employed to screen the blank SNEDDS, using emulsifying rate and particle size as evaluation indices. Ternary phase diagrams were then constructed to investigate the effects of drug loading on the self-emulsifying performance of the optimized blank SNEDDS. Subsequently, in vivo pharmacokinetic parameters of the morin-phospholipid complex self-nanoemulsifying drug delivery system (MPC-SNEDDS) were investigated in Wistar rats (200 mg/kg of morin by oral administration).
Results: The optimum formulation was composed of Labrafil® M 1944 CS, Cremophor® RH 40, and Transcutol® P (3:5:3, w/w), which gave a mean particle size of approximately 140 nm. Oral delivery of the MPC-SNEDDS exhibited a significantly greater Cmax (28.60 µg/mL) than the morin suspension (5.53 µg/mL) or MPC suspension (23.74 µg/mL) (all P < 0.05). Tmax was prolonged from 0.48 to 0.77 hours and to 1 hour for MPC and MPC-SNEDDS, respectively. In addition, the relative oral bioavailability of morin formulated in the MPC-SNEDDS was 6.23-fold higher than that of the morin suspension, and was significantly higher than that of the MPC suspension (P < 0.05).
Conclusion: The study demonstrated that a SNEDDS combined with the phospholipid complex technique was a promising strategy to enhance the oral bioavailability of morin.

Keywords: morin, phospholipid complex, self-nanoemulsifying drug delivery system, oral bioavailability


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