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Nanoemulsion improves the oral bioavailability of baicalin in rats: in vitro and in vivo evaluation.

Zhao L, Wei Y, Huang Y, He B, Zhou Y, Fu J - Int J Nanomedicine (2013)

Bottom Line: After dilution 30-fold with water, the solubilization capacity of BAN-1 and BAN-2 did not change.In vitro release results showed sustained-release characteristics.In conclusion, these results demonstrated that the baicalin-loaded nanoemulsion formulation, in particular BAN-1, was very effective for improving the oral bioavailability of baicalin and exhibited great potential for future clinical application.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Luzhou Medical College, Luzhou City, Sichuan Province, People's Republic of China ; Drug and Functional Food Research Center, Luzhou Medical College, Luzhou City, Sichuan Province, People's Republic of China.

ABSTRACT
Baicalin is one of the main bioactive flavone glucuronides derived as a medicinal herb from the dried roots of Scutellaria baicalensis Georgi, and it is widely used for the treatment of fever, inflammation, and other conditions. Due to baicalin's poor solubility in water, its absolute bioavailability after oral administration is only 2.2%. The objective of this study was to develop a novel baicalin-loaded nanoemulsion to improve the oral bioavailability of baicalin. Based on the result of pseudoternary phase diagram, the nanoemulsion formulation consisting of soy-lecithin, tween-80, polyethylene glycol 400, isopropyl myristate, and water (1:2:1.5:3.75:8.25, w/w) was selected for further study. Baicalin-loaded nanoemulsions (BAN-1 and BAN-2) were prepared by internal or external drug addition and in vivo and in vitro evaluations were performed. The results showed that the mean droplet size, polydispersity index, and drug content of BAN-1 and BAN-2 were 91.2 ± 2.36 nm and 89.7 ± 3.05 nm, 0.313 ± 0.002 and 0.265 ± 0.001, and 98.56% ± 0.79% and 99.40% ± 0.51%, respectively. Transmission electron microscopy revealed spherical globules and confirmed droplet size analysis. After dilution 30-fold with water, the solubilization capacity of BAN-1 and BAN-2 did not change. In vitro release results showed sustained-release characteristics. BAN-1 formulation was stable for at least 6 months and was more stable than BAN-2. In rats, the area under the plasma drug concentration-time curve value of BAN-1 was 1.8-fold and 7-fold greater than those of BAN-2 and free baicalin suspension after oral administration at a dose of 100 mg/kg. In conclusion, these results demonstrated that the baicalin-loaded nanoemulsion formulation, in particular BAN-1, was very effective for improving the oral bioavailability of baicalin and exhibited great potential for future clinical application.

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Solubility of baicalin in various oil phases and cosurfactants.Note: Data are expressed as mean ± standard deviation (n = 3).Abbreviations: IPM, isopropyl myristate; IPP, isopropyl palmitate; PEG400, polyethylene glycol 400.
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f2-ijn-8-3769: Solubility of baicalin in various oil phases and cosurfactants.Note: Data are expressed as mean ± standard deviation (n = 3).Abbreviations: IPM, isopropyl myristate; IPP, isopropyl palmitate; PEG400, polyethylene glycol 400.

Mentions: For nanoemulsion formulations, oil phase is an important ingredient that can solubilize lipophilic drugs and enhance the amount of lipophilic drug transported through the intestinal lymphatic system. Therefore, the solubility of drug in oil phase is crucial for the development of nanoemulsion formulations. The solubilities of baicalin in oil phase, including glyceryl monooleate, IPM, and IPP, were investigated (Figure 2). Among these oil phases, the highest solubilization capacity was observed in IPM (0.0138 ± 0.0036 mg/mL), followed by glyceryl monooleate (0.0054 ± 0.0009 mg/mL) and IPP (0.0039 ± 0.0007 mg/mL). In addition, IPM was widely used to develop oral nanoemulsion formulations.33 As a result, IPM was chosen for further investigation in this study. Cosurfactant was also an important component for the development of nanoemulsion formulations, because a suitable cosurfactant is used to overcome problems related to the poor solubility and low oral bioavailability of drug.11 Thus, the solubilities of baicalin in three different cosurfactants were studied (Figure 2). Among the cosurfactants examined, PEG400 showed the highest solubility of baicalin (9.328 ± 0.259 mg/mL), followed by propylene glycol (7.056 ± 0.308 mg/mL); ethanol showed the lowest solubility (1.214 ± 0.115 mg/mL). To increase drug-loading efficiency, in combination with evaporation of ethanol, PEG400 and propylene glycol were selected as cosurfactants for further investigation.


Nanoemulsion improves the oral bioavailability of baicalin in rats: in vitro and in vivo evaluation.

Zhao L, Wei Y, Huang Y, He B, Zhou Y, Fu J - Int J Nanomedicine (2013)

Solubility of baicalin in various oil phases and cosurfactants.Note: Data are expressed as mean ± standard deviation (n = 3).Abbreviations: IPM, isopropyl myristate; IPP, isopropyl palmitate; PEG400, polyethylene glycol 400.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3794992&req=5

f2-ijn-8-3769: Solubility of baicalin in various oil phases and cosurfactants.Note: Data are expressed as mean ± standard deviation (n = 3).Abbreviations: IPM, isopropyl myristate; IPP, isopropyl palmitate; PEG400, polyethylene glycol 400.
Mentions: For nanoemulsion formulations, oil phase is an important ingredient that can solubilize lipophilic drugs and enhance the amount of lipophilic drug transported through the intestinal lymphatic system. Therefore, the solubility of drug in oil phase is crucial for the development of nanoemulsion formulations. The solubilities of baicalin in oil phase, including glyceryl monooleate, IPM, and IPP, were investigated (Figure 2). Among these oil phases, the highest solubilization capacity was observed in IPM (0.0138 ± 0.0036 mg/mL), followed by glyceryl monooleate (0.0054 ± 0.0009 mg/mL) and IPP (0.0039 ± 0.0007 mg/mL). In addition, IPM was widely used to develop oral nanoemulsion formulations.33 As a result, IPM was chosen for further investigation in this study. Cosurfactant was also an important component for the development of nanoemulsion formulations, because a suitable cosurfactant is used to overcome problems related to the poor solubility and low oral bioavailability of drug.11 Thus, the solubilities of baicalin in three different cosurfactants were studied (Figure 2). Among the cosurfactants examined, PEG400 showed the highest solubility of baicalin (9.328 ± 0.259 mg/mL), followed by propylene glycol (7.056 ± 0.308 mg/mL); ethanol showed the lowest solubility (1.214 ± 0.115 mg/mL). To increase drug-loading efficiency, in combination with evaporation of ethanol, PEG400 and propylene glycol were selected as cosurfactants for further investigation.

Bottom Line: After dilution 30-fold with water, the solubilization capacity of BAN-1 and BAN-2 did not change.In vitro release results showed sustained-release characteristics.In conclusion, these results demonstrated that the baicalin-loaded nanoemulsion formulation, in particular BAN-1, was very effective for improving the oral bioavailability of baicalin and exhibited great potential for future clinical application.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Luzhou Medical College, Luzhou City, Sichuan Province, People's Republic of China ; Drug and Functional Food Research Center, Luzhou Medical College, Luzhou City, Sichuan Province, People's Republic of China.

ABSTRACT
Baicalin is one of the main bioactive flavone glucuronides derived as a medicinal herb from the dried roots of Scutellaria baicalensis Georgi, and it is widely used for the treatment of fever, inflammation, and other conditions. Due to baicalin's poor solubility in water, its absolute bioavailability after oral administration is only 2.2%. The objective of this study was to develop a novel baicalin-loaded nanoemulsion to improve the oral bioavailability of baicalin. Based on the result of pseudoternary phase diagram, the nanoemulsion formulation consisting of soy-lecithin, tween-80, polyethylene glycol 400, isopropyl myristate, and water (1:2:1.5:3.75:8.25, w/w) was selected for further study. Baicalin-loaded nanoemulsions (BAN-1 and BAN-2) were prepared by internal or external drug addition and in vivo and in vitro evaluations were performed. The results showed that the mean droplet size, polydispersity index, and drug content of BAN-1 and BAN-2 were 91.2 ± 2.36 nm and 89.7 ± 3.05 nm, 0.313 ± 0.002 and 0.265 ± 0.001, and 98.56% ± 0.79% and 99.40% ± 0.51%, respectively. Transmission electron microscopy revealed spherical globules and confirmed droplet size analysis. After dilution 30-fold with water, the solubilization capacity of BAN-1 and BAN-2 did not change. In vitro release results showed sustained-release characteristics. BAN-1 formulation was stable for at least 6 months and was more stable than BAN-2. In rats, the area under the plasma drug concentration-time curve value of BAN-1 was 1.8-fold and 7-fold greater than those of BAN-2 and free baicalin suspension after oral administration at a dose of 100 mg/kg. In conclusion, these results demonstrated that the baicalin-loaded nanoemulsion formulation, in particular BAN-1, was very effective for improving the oral bioavailability of baicalin and exhibited great potential for future clinical application.

Show MeSH
Related in: MedlinePlus