Ampelopsin, one of the most common flavonoids, reported to possess numerous pharmacological activities and shows poor aqueous solubility. The purpose of this study was to enhance the dissolution rate and bioavailability of this drug by developing a novel delivery system that is microemulsion (ME) and to study the effect of microemulsion (ME) on the oral bioavailability of ampelopsin. Capmul MCM-based ME formulation with Cremophor EL as surfactant and Transcutol as cosurfactant was developed for oral delivery of ampelopsin. Optimised ME was evaluated for its transparency, viscosity, percentage assay and so forth. Solubilisation capacity of the ME system was also determined. The prepared ME was compared with the pure drug solution and commercially available tablet for in vitro drug release. The optimised ME formulation containing ampelopsin, Capmul MCM (5.5%), Cremophor EL (25%), Transcutol P (8.5%), and distilled water showed higher in vitro drug release, as compared to plain drug suspension and the suspension of commercially available tablet. These results demonstrate the potential use of ME for improving the bioavailability of poor water soluble compounds, such as ampelopsin. 1. Introduction Ampelopsin, isolated from the tender stem and leaves of the plant species Ampelopsis grossedentata (Hand-Mazz)？ ？W. T. Wang, was one of the most common flavonoids (Figure 1). Ampelopsin was reported to possess numerous pharmacological activities, such as anti-inflammatory, antimicrobial activity, relieving cough, antioxidation, antihypertension, hepatoprotective effect and anticarcinogenic effect [1–4]. However, the ampelopsin has very less solubility in water (0.2？mg/mL at 25°C), it has very low permeability through intestinal mucosa [5]. Microemulsion (ME), a novel drug delivery system, has been reported to improve the rate and extent of absorption of lipophilic drugs. As a modern drug carrier system, microemulsions are defined as single optically isotropic and thermodynamically stable solution with droplet sizes in the submicron range. In general, they consist of an oil phase, a surfactant, a cosurfactant, and an aqueous phase. Some advantages offered by microemulsions include improvement in drug solubility, enhancement of bioavailability, protection of the drug against the environment, ease of manufacturing, and a long shelf life [6–13]. Use of ampelopsin in most pharmaceutical preparations and some research experiments was thereby limited due to its low water solubility, low intestine permeability and degradation in solution. To our knowledge, no information
References
[1]
J. Ye, Y. Guan, S. Zeng, and D. Liu, “Ampelopsin prevents apoptosis induced by H2O2 in MT-4 lymphocytes,” Planta Medica, vol. 74, no. 3, pp. 252–257, 2008.
[2]
G. Y. TAN, M. H. ZHANG, J. H. FENG, A. Y. HAN, S. S. ZHENG, and P. XIE, “Effects of pretreatment by the flavanol ampelopsin on porcine kidney epithelial cell injury induced by hydrogen peroxide,” Agricultural Sciences in China, vol. 9, no. 4, pp. 598–604, 2010.
[3]
S. Qi, Y. Xin, Y. Guo et al., “Ampelopsin reduces endotoxic inflammation via repressing ROS-mediated activation of PI3K/Akt/NF-κB signaling pathways,” International Immunopharmacology, vol. 12, no. 1, pp. 278–287, 2012.
[4]
T. Kundakovi？, T. Stanojkovi？, M. Milenkovi？ et al., “Cytotoxic, antioxidant, and antimicrobial activities of Ampelopsis brevipedunculata and Parthenocissus tricuspidata (Vitaceae),” Archives of Biological Sciences, vol. 60, no. 4, pp. 641–647, 2008.
[5]
L. P. Ruan, B. Y. Yu, G. M. Fu, and D. N. Zhu, “Improving the solubility of ampelopsin by solid dispersions and inclusion complexes,” Journal of Pharmaceutical and Biomedical Analysis, vol. 38, no. 3, pp. 457–464, 2005.
[6]
Ajazuddin and S. Saraf, “Applications of novel drug delivery system for herbal formulations,” Fitoterapia, vol. 81, no. 7, pp. 680–689, 2010.
[7]
X. Dong, X. Ke, and Z. Liao, “The microstructure characterization of meloxicam microemulsion and its influence on the solubilization capacity,” Drug Development and Industrial Pharmacy, vol. 37, no. 8, pp. 894–900, 2011.
[8]
C. Malcolmson and M. J. Lawrence, “Three-component non-ionic oil-in-water microemulsions using polyoxyethylene ether surfactants,” Colloids and Surfaces B, vol. 4, no. 2, pp. 97–109, 1995.
[9]
P. P. Constantinides, J. P. Scalart, C. Lancaster et al., “Formulation and intestinal absorption enhancement evaluation of water-in-oil microemulsions incorporating medium-chain glycerides,” Pharmaceutical Research, vol. 11, no. 10, pp. 1385–1390, 1994.
[10]
F. Lopez, G. Cinelli, L. Ambrosone, G. Colafemmina, A. Ceglie, and G. Palazzo, “Role of the cosurfactant in water-in-oil microemulsion: interfacial properties tune the enzymatic activity of lipase,” Colloids and Surfaces A, vol. 237, no. 1–3, pp. 49–59, 2004.
[11]
B. Brime, M. A. Moreno, G. Frutos, P. Ballesteros, and P. Frutos, “Amphotericin B in oil-water lecithin-based microemulsions: formulation and toxicity evaluation,” Journal of Pharmaceutical Sciences, vol. 91, no. 4, pp. 1178–1185, 2002.
[12]
A. A. Badawi, S. A. Nour, W. S. Sakran, and S. M. S. El-Mancy, “Preparation and evaluation of microemulsion systems containing salicylic acid,” AAPS PharmSciTech, vol. 10, no. 4, pp. 1081–1084, 2009.
[13]
P. K. Ghosh, R. J. Majithiya, M. L. Umrethia, and R. S. R. Murthy, “Design and development of microemulsion drug delivery system of acyclovir for improvement of oral bioavailability,” AAPS PharmSciTech, vol. 7, no. 3, article 77, pp. E172–E177, 2006.
[14]
A. K. Singh, A. Chaurasiya, A. Awasthi et al., “Oral bioavailability enhancement of exemestane from self-microemulsifying drug delivery system (SMEDDS),” AAPS PharmSciTech, vol. 10, no. 3, pp. 906–916, 2009.
[15]
J. G. Yang, B. G. Liu, G. Z. Liang, and Z. X. Ning, “Structure-activity relationship of flavonoids active against lard oil oxidation based on quantum chemical analysis,” Molecules, vol. 14, no. 1, pp. 46–52, 2009.
[16]
Y. S. Zhang, Z. X. Ning, S. Z. Yang, and H. Wu, “Antioxidation properties and mechanism of action of dihydromyricetin from Ampelopsis grossedentata,” Yaoxue Xuebao, vol. 38, no. 4, pp. 241–244, 2003.
[17]
X. Li, Q. Yuan, Y. Huang, Y. Zhou, and Y. Liu, “Development of silymarin self-microemulsifying drug delivery system with enhanced oral bioavailability,” AAPS PharmSciTech, vol. 11, no. 2, pp. 672–678, 2010.
