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Icariin as a hepatoprotector from Herba epimedii can expand the cardiovascular and cerebral blood vessels, promote hematopoietic functions, enhance the immune system and show anti-liver tumor activities. However, its low solubility (0.02 mg/mL) limits its clinical applications as food and medical supplements. Through complexation with HP-γ-cyclodextrin by using a trace amount of water-soluble polymer, the water solubility of icariin was increased by 654 times, which is the best result to date for the water solubility study of icariin. In an in vitro pharmacokinetic study, the complexation increased the dissolution rate of icariin by 80 times, and the icariin complex can be 100% released in the first few minutes. Through complexation, in an in vivo dog pharmacokinetic study, the Cmax of icariin was increased about 5 times, the AUC0-120 was increased about 20 times and the clearance of icariin was changed from 11.17 L/h/kg to 0.65 L/h/kg. The half-life time was changed from 0.68 h to 6.38 h and the relative bioavailability was increased by nearly 20 times, indicating that less drug is needed for the same therapeutic effect by using the icariin complex, and the complex can be used as a potential potent hepatoprotector or anti-liver cancer drug.

Albendazole is the preferred deworming drug and has strong insecticidal effects on human and animal helminth parasites, showing remarkable activity against hepatocellular carcinoma and colorectal cancer cells. However, it is classified as being in class II in the Biopharmaceutics Classification System due to its poor water solubility (0.2 mg/L) and high permeability, which make the clinical application of albendazole impractical. Through complexation with methyl-β-cyclodextrin, as the best result so far, albendazole’s water solubility was increased by 150,000 times, and albendazole could be 90% released during the first 10 min. In an in vivo pharmacokinetic study, the Cmax and Tmax of the active metabolized sulfoxide were changed from 2.81 µg/mL at 3 h to 10.2 µg/mL at 6 h and the AUC0–48 was increased from 50.72 h⁎μg/mL to 119.95 h⁎μg/mL, indicating that the inclusion complex obtained can be used as a new oral therapeutic anti-anthelmintic and anti-tumor agent formulation.

Since griseofulvin was marketed as a non-polyene antifungal antibiotic drug in 1958, its poor water solubility has been an issue for its wide applications, and over the last sixty years, many attempts have been made to increase its water solubility; however, a significant result has yet to be achieved. Through supercritical carbon dioxide-assisted cyclodextrin complexation with the addition of a trace amount of water-soluble polymer surfactant, the griseofulvin inclusion complex with HP-γ-cyclodextrin was prepared and confirmed. The 1:2 ratio of griseofulvin and HP-γ-cyclodextrin in the complex was determined based on its NMR study. After complexation with HP-γ-cyclodextrin, griseofulvin’s water solubility was increased 477 times compared with that of griseofulvin alone, which is the best result thus far. The complex showed 90% of griseofulvin release in vitro in 10 min, in an in vivo dog pharmacokinetic study; the Cmax was increased from 0.52 µg/mL to 0.72 µg/mL, AUC0–12 was increased from 1.55 μg·h/mL to 2.75 μg·h/mL, the clearance was changed from 51.78 L/kg/h to 24.16 L/kg/h, and the half-life time was changed from 0.81 h to 1.56 h, indicating the obtained griseofulvin complex can be a more effective drug than griseofulvin alone.