Effect of β-cyclodextrin and Hydroxypropyl β-cyclodextrin on Aqueous Stability, Solubility and Dissolution of Novel Anti-cancer Drug Rigosertib

Abstract

Aim: To study Effect of β-cyclodextrin and hydroxypropyl β-cyclodextrin on aqueous stability, solubility and dissolution of novel anti-cancer drug Rigosertib. Methods: β-cyclodextrin and hydroxypropyl β-cyclodextrin were used to form complex with Rigosertib. The effect of cyclodextrins on drug solubility was studied using phase solubility method. Physico-chemical characterization of drug cyclodextrin complex was performed using differential scanning calorimeter, X-Ray diffraction, Infrared spectroscopy and Scanning electron microscopy. Dissolution profiles of drug-cyclodextrin complexes showed better drug release compared to untreated drug in pH 1, 2, 4 and 5.5 dissolution medium.    Results: Rigosertib exhibits poor solubility and chemical instability in acidic solutions. Poor aqueous stability along with limited solubility in acidic conditions can result in limited oral bioavailability of the drug. Both analogues showed positive effect on drug solubility. Hydroxypropyl β-cyclodextrin performed better compared to β-cyclodextrin to improve drug solubility. In addition, presence of both cyclodextrin analogues improved drug stability in acidic solutions. Physico-chemical characterization of drug cyclodextrin complex was performed using differential scanning calorimeter, X-Ray diffraction, Infrared spectroscopy and Scanning electron microscopy. Dissolution profiles of drug-cyclodextrin complexes showed better drug release compared to untreated drug in pH 1, 2, 4 and 5.5 dissolution medium.    Conclusion: Improved drug solubility and chemical stability in acidic conditions can be attributed to complex formation between drug and cyclodextrin.