Enrofloxacin, a third-generation fluoroquinolone, is a broad-spectrum antimicrobial drug against a lot of veterinary bacterial diseases. However, bactericidal activity of enrofloxacin is concentration-dependent and its poor aqueous solubility and bitter taste limit its development and application. Meanwhile, 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), a widely used cyclodextrin analog, is a safe and an effective drug carrier. It forms inclusion complexes with its drug substrates and improves their physiochemical and pharmacokinetic properties. Enrofloxacin was also found to form a stable inclusion complex with HP-β-CD and different research groups have shown improved solubility for enrofloxacin by 32.5%, 9.25 and 165-fold. Our own efforts in this direction resulted in manifold improvement (916-fold) in its solubility compared to the previous studies. It was further shown that pharmaceutical properties, absorption and bioavailability, of enrofloxacin have also been significantly improved by complexation with HP-β-CD.

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 C_max of icariin was increased about 5 times, the AUC_0-120 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 C_max and T_max 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 AUC_0–48 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.

As a powerful imidazole antifungal drug, ketoconazole’s low solubility (0.017 mg/mL), together with its odor and irritation, limited its clinical applications. The inclusion complex of ketoconazole with randomly methylated β-cyclodextrin was prepared by using an aqueous solution method after cyclodextrin selection through phase solubility studies, complexation methods, and condition selection through single factor and orthogonal strategies. The complex was confirmed by FTIR (Fourier-transform infrared spectroscopy), DSC (differential scanning calorimetry), TGA (thermogravimetric analysis), SEM (scanning electron microscope images), and NMR (Nuclear magnetic resonance) studies. Through complexation, the water solubility of ketoconazole in the complex was increased 17,000 times compared with that of ketoconazole alone, which is the best result so far for the ketoconazole water solubility study. In in vitro pharmacokinetic studies, ketoconazole in the complex can be 100% released in 75 min, and in in vivo pharmacokinetic studies in dogs, through the complexation, the C_max was increased from 7.56 μg/mL to 13.58 µg/mL, and the AUC_0~72 was increased from 22.69 μgh/mL to 50.19 μgh/mL, indicating that this ketoconazole complex can be used as a more efficient potential new anti-fungal drug.