Development of Orally Disintegrating Tablets from Solid Dispersions Containing Tolvaptan/Cyclodextrin Complexes

Tolvaptan is a compound that is practically insoluble in water and poorly soluble at physiological pH, and is used to treat low blood sodium levels in adults with conditions such as heart failure and certain hormonal imbalances. Increasing the water solubility and dissolution rate of tolvaptan could increase its bioavailability and, consequently, its efficacy. This study aimed to increase the efficiency of tolvaptan by enhancing its solubility and dissolution rate, and to develop a fast-acting dosage form that improves convenience for patients with swallowing difficulties.

Solid dispersion (SD) formulations were developed by the rotary evaporation method using hydrophilic polymers (polyvinylpyrrolidone and polyethylene oxide), solubility enhancers (Solutol HS-15 and Gelucire 44/14), and complexing agents (β-cyclodextrin and hydroxypropyl-β-cyclodextrin). Various characterization studies were performed on developed formulations, including solubility studies, X-ray diffraction, differential scanning calorimetry, Fourier transform infrared spectroscopy, and scanning electron microscopy analyses, in vitro dissolution tests, and release kinetics studies.

The solubility of tolvaptan in the 2-hydroxypropyl-beta-cyclodextrin (HPβCD)-SD2 formulation containing HPβCD, was the highest at 0.2314 mg/mL, which was approximately 8.7 times that of pure tolvaptan. Based on the results, HPβCD was selected as the complexing agent as the optimal SD formulation. In the dissolution study, at least 90% of the tolvaptan in the HPβCD-SD2 formulation dissolved in all buffer solutions within 25 min. Orally disintegrating tablets (ODTs) were prepared using the HPβCD-SD2 formulation; formulation code 59, which had a friability of ≤1% and a disintegration time of ≤180 s, was selected as the final tablet.

A new SD formulation with increased solubility and dissolution rate compared with pure tolvaptan was developed. The developed ODTs may be an alternative to the current commercial product.