Solubility Of Baicalein Research Articles

Preparation and characterization of baicalein/hydroxypropyl-β-cyclodextrin inclusion complex for enhancement of solubility, antioxidant activity and antibacterial activity using supercritical antisolvent technology

In this study, the preparation of an inclusion complex of baicalein (BAI) and hydroxypropyl-β-cyclodextrin (HP-β-CD) using the precipitation with compressed antisolvents (PCA) process was studied. The goal was to improve the solubility, antioxidant activity, antibacterial activity and bioavailability of BAI, an active component in traditional herbal medicines. DSC, XRD, and SEM results confirmed the formation of an inclusion complex between BAI and HP-β-CD. The solubility of BAI in the BAI/HP-β-CD inclusion complex improved remarkably. A relatively high BAI solubility of 147.38 μg/mL was reported in the inclusion complex (particle size = 0.295 μm) formed under the following conditions (pressure = 14 MPa, temperature = 318 K, mole ratio of BAI/HP-β-CD = 1:2). Both in vitro and in vivo study, proved the bioavailability enhancement of BAI by a supercritical antisolvent process via coprecipitation with HP-β-CD. After efficient complexation using the PCA process, the limited antioxidant activity and antibacterial activity of BAI was highly enhanced together with the aqueous solubility. Hence, this study provides valuable information for the potential clinical application of inclusion complexes of BAI using the PCA process.

Solubility and thermodynamic properties of baicalein in water and ethanol mixtures from 283.15 to 328.15 K

Baicalein is a traditional Chinese medicine with multiple pharmacological effects, including anti-inflammatory activity, anti-pathogen activity, antitumor activity and neuroprotective activity. However, due to the limited solubility and poor stability in aqueous solution, its clinical application is greatly compromised. Here, we investigated the solubility and thermodynamic properties of baicalein in a binary system of water and ethanol from 283.15 K to 328.15 K (common temperature in labs and pharmaceutical industry), in order to optimize the extraction and purification process of baicalein. The results showed that the experimental solubility of baicalein increased with the increased ethanol ratio in the binary system and with the rising temperature. Six models, the ideal mixture model, the polynomial empirical equation, the Apelblat equation, the Buchowski–Ksiazczak (λh) equation, the general single model and the combination of Jouyban–Acree and van’t Hoff models, were chosen to correlate with the experimental data. The correlated results of the general single model were in good agreement with the experimentally measured solubility data with root mean square deviations (%) in the range of 0.22–1.06 In addition, its thermodynamic property implied that the dissolution process of baicalein under the studied conditions is a non-spontaneous endothermic process.

Comments on “Solubility of Baicalein in Different Solvents from (287 to 323) K”

Inconsistencies were identified in the reported equation parameters by Wu et al. (Int J Thermophys 35:1465–1475, 2014) for describing the baicalein solubility in eight organic solvents with the van’t Hoff equation and modified Apelblat equation. The reported model parameters do not correspond with the reported solubility. The parameters of the two equations were reevaluated.

Inclusion complexes of cysteinyl β-cyclodextrin with baicalein restore collagen synthesis in fibroblast cells following ultraviolet exposure.

Baicalein, a bioactive flavonoid, has poor water solubility, thereby limiting its use in a wide range of biological applications. In the present study, we used inclusion complexes of cysteinyl β-cyclodextrin (β-CD) with baicalein to enhance the stability and solubility of baicalein in aqueous solution. We examined the effects of inclusion complexes of cysteinyl β-CD on collagen synthesis following ultraviolet (UV) irradiation, as well as the mechanisms underlying its effects. Our findings demonstrated that baicalein significantly restored collagen synthesis in the UV-exposed human fibroblast Hs68 cells. In addition, synthetic cysteine functionalized β-CDs were found to promote baicalein-induced collagen synthesis. Inclusion complexes of cysteinyl β-CDs with baicalein significantly upregulated the protein expression of type I collagen and activated the transcription of type I, II, and III collagen. Inclusion complexes of cysteinyl β-CDs with baicalein also downregulated matrix metalloproteinase -1 and -3, and α-smooth muscle actin expression. In addition, inclusion complexes of cysteinyl β-CDs with baicalein attenuated the expression of caveolin-1, but this treatment enhanced the UV-induced phosphorylation of Smad in the transforming growth factor-β pathway. These results suggested that the newly synthesized derivative of CD can be used as a complexing agent to enhance the bioavailability of flavonoids such as baicalein, especially in restoring collagen synthesis.

A strategy to improve the oral availability of baicalein: The baicalein-theophylline cocrystal

Baicalein (BE) is a flavonoid compound derived from the roots of Scutellaria baicalensis. It has widely been used as anti-oxidant, anti-virus, anti-bacteria, anti-inflammatory and anti-allergic therapies. Due to its poor water solubility (16.82 μg/ml), the therapeutic effectiveness and oral bioavailability of Baicalein are highly limited. The purpose of this study was to investigate the possibility of baicalein-theophylline (BE-TH) cocrystals to achieve the simultaneous enhancement in dissolution and oral bioavailability of BE. The cocrystal had the new characteristic of scanning electron microscopy, differential scanning calorimetry thermograms and X-ray powder diffraction. Compared with coarse powder of BE, BE-TH cocrystals had significantly improved the solubility of BE. The dissolution test showed that the BE-TH cocrystals demonstrated 2.2-fold and 7.1-fold higher rate of dissolution than that of BE coarse powder in HCl (pH = 1.2) and phosphate buffer (PBS, pH = 6.8), respectively. Moreover, the cocrystals exhibited a 5.86-fold higher area under the curve in rats after the oral administration. This investigation enriched the present understanding of cocrystals on their behavior in vitro and in vivo, and built the groundwork for future development of BE as a promising compound into efficacious drug products.

Solubility of Baicalein in Different Solvents from (287 to 323) K

The solubility of baicalein in methanol, ethanol, n-propanol, propan-2-ol, n-butanol, isobutyl alcohol, 1,3-propanediol, and ethyl acetate was measured from (287 to 323) K at atmospheric pressure using high-performance liquid chromatography analysis. Its corresponding (solid + liquid) equilibrium data should provide essential support for the purification of baicalein. The solubility data were correlated by the modified Apelblat equation and the van’t Hoff equation. The solubility data indicated that ethyl acetate might be the best choice for purification of baicalein among these solvents. The correlated results showed that the two equations were both in good agreement with the experimental values, but the correlation of the modified Apelblat equation had smaller deviations than those of the van’t Hoff equation.

Preparation and evaluation of self-microemulsifying drug delivery system of baicalein

The main object of this work is to prepare self-microemulsifying drug delivery system (SMEDDS) for oral bioavailability enhancement of a poorly water-soluble drug, baicalein. SMEDDS is the mixture of surfactants, cosurfactants, and oils, which are emulsified in aqueous media under conditions of gentle agitation or gastrointestinal motility. Solubility of baicalein was determined in various vehicles. Pseudo-ternary phase diagrams were constructed to identify the efficient self-emulsification region and droplet size distributions of the resultant microemulsions were determined using a particle size analyzer. Optimized SMEDDS formulations for baicalein were Cremophor RH40 (53.57%) as surfactant, Transcutol P (21.43%) as cosurfactant, and Caprylic capric triglyceride (ODO, 25%) as oil. The drug release rate of SMEDDS was significantly higher than that of the baicalein suspension. Comparison of the pharmacokinetics between baicalein-loaded SMEDDS and baicalein suspension was also performed in rats. The plasma concentrations of baicalein and baicalin, its mainly conjugated metabolite, were determined by HPLC method. The in vivo results showed that the absorption of baicalein from SMEDDS resulted in about 200.7% increase in relative bioavailability compared with that of the baicalein suspension. Our studies illustrated the potential use of SMEDDS for the delivery of hydrophobic compounds, such as baicalein by the oral route.

Ocular Pharmacokinetics and Availability of Topically Applied Baicalein in Rabbits

Purpose: To evaluate the ocular pharmacokinetics and availability of baicalein following topical application. Methods: Hydroxypropyl beta-cyclodextrin (HP-β -CD) was used to formulate an aqueous eye drop to improve aqueous solubility of baicalein. A single dose of either baicalein suspension (1%) (Bai-SP) or baicalein (1%)/HP-β -CD (10%) solution (Bai-CD) was topically applied to rabbits. Aqueous humor and cornea were collected after 5, 10, 20, 30, 45, 60, 90, and 120 min. Baicalein concentrations were determined by high-performance liquid chromatography (HPLC) after extraction. Results: After topically applying Bai-CD, the baicalein concentrations in aqueous humor were significantly increased at 20–120 min except at 90 min compared with those of Bai-SP (p < 0.05). The highest levels of baicalein in aqueous humor (Cmax, 4.11 ± 0.75 μ g/ml) were obtained after 30 min application of Bai-CD, 3.6 times greater than that corresponding to the Bai-SP at 20 min. The Bai-CD produced an over 2.1-fold bioavailability (AUC0−120, area under the concentration time curve between 0 and 120 min) increase in aqueous humor compared to the Bai-SP. Peak baicalein concentration in cornea (56.53 ± 17.02 μ g/g) was achieved within 5 min after topical application of Bai-CD and 4.5 times higher than that of Bai-SP at the same timepoint. The baicalein levels in corneas obtained after application of Bai-CD were all much higher than those obtained by Bai-SP (p < 0.01), whereas the drug levels became undetectable 30 min after topical application of Bai-SP. Conclusion: Bai-CD formulation is superior to Bai-SP for increasing ocular bioavailability.