Highly Water-Soluble Solid Dispersions of Honokiol: Preparation, Solubility, and Bioavailability Studies and Anti-Tumor Activity Evaluation

Abstract

Honokiol (HK), a well-tolerated natural product, has many multiple pharmacological activities. However, its poor water solubility and low bioavailability limit its clinical application and development. The aim of this research was to prepare the solid dispersion (SD) formulation of honokiol (HK) with poloxamer-188 (PLX) as the carrier, thereby improving its solubility and oral bioavailability. Firstly, by investigating the relationship between the addition amount of the PLX and the solubility of HK, and the effects of solid dispersions with different ratios of HK–PLX on the solubility of HK, we determined that the optimum ratio of PLX to HK was (1:4). Then, the HK–PLX (1:4) SD of HK was prepared using the solvent evaporation method. The morphology of the obtained HK–PLX (1:4) SD was different from that of free HK. The HK in the HK–PLX (1:4) SD existed in amorphous form and formed intermolecular hydrogen bonds with PLX. Additionally, the solubility values of the HK–PLX (1:4) SD were about 32.43 ± 0.36 mg/mL and 34.41 ± 0.38 mg/mL in artificial gastric juice (AGJ) and in artificial intestinal juice (AIJ), respectively. Compared with free HK, the release rate and the bioavailability was also substantially improved for HK in its SD form. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay indicated that the HK–PLX (1:4) SD showed higher inhibition of HepG2 cells than free HK. Taken together, the present study suggests that the HK–PLX (1:4) SD could become a new oral drug formulation with high bioavailability and could produce a better response for clinical applications of HK.

Magnolol and Honokiol: Two Natural Compounds with Similar Chemical Structure but Different Physicochemical and Stability Properties

“…In the case of honokiol, no data about its solubility at different pH values have been found in the available literature. A solubility of 14 µg/mL of honokiol in water has been reported [38], which is lower than that obtained in this work (50.6 µg/mL). Again, the discrepancy in these values could be related to the agitation time (4 h vs. 24 h).…”

Enhanced Dissolution of Luteolin by Solid Dispersion Prepared by Different Methods: Physicochemical Characterization and Antioxidant Activity

“…The beaker was kept in a water bath held at 60 °C to evaporate the organic solvent. The organic solvents from the SDs are usually evaporated using a rotary evaporator in order to prevent the release in the environment. , Nevertheless, in the preparation of SDs of drugs, organic solvents are evaporated completely with a rapid evaporation rate, which cannot be achieved using a rotary evaporator. For the rapid evaporation of organic solvents from SDs, some other techniques such as water bath or tray dryer have been used. , Therefore, the SDs of LT were prepared in beakers, which were subjected to water bath for the evaporation of organic solvents instead of using a rotary evaporator. ,, The preparation was cooled in ice and solidified for 12 h, and the obtained mass was stored and then pulverized using a pestle and mortar.…”

Pharmacokinetics of five phthalides in volatile oil of Ligusticum sinense Oliv.cv. Chaxiong, and comparison study on physicochemistry and pharmacokinetics after being formulated into solid dispersion and inclusion compound

“…The absorption of SA, NBP, NOL, ZL and BP were rapid, with peak concentrations occurring before 30 min after oral administration. Among them, the T max of SA, NOL and ZL were about 12 min, which meant they absorbed more quickly than NBP and BP [ 32 , 33 ]. Compared with intravenous injection, its peak concentration was lower, and the absolute bioavailability of the five components was less than 25%, which was partly because of extensive first-pass metabolism in the liver [ 39 , 40 ].…”

“…The solvent was removed under vacuum in a rotary evaporator at 40 °C and 45 rpm for 2 h, and the resulting dispersion was kept in refrigerator at − 80 °C. After 4 h, the dispersion was crushed and sieved through 40-mesh, and stored in a desiccator at room temperature for use [ 32 , 33 ].…”

“…Oral bioavailability of LIG was low (2.6%), and seven metabolites of LIG were unequivocally characterized as NBP, senkyunolide I and senkyunolide H [ 40 ]. The pharmacokinetic parameters of SA, NBP and ZL showed significant differences between Rhizoma Chuanxiong group and the combination of Radix Angelicae Dahuricae and Rhizoma Chuanxiong group ( P < 0.05) [ 32 , 33 ]. The i.v.…”