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

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems

Background:

• Tolvaptan exhibits poor water solubility, limiting its bioavailability and efficacy.
• Enhancing tolvaptan's solubility and dissolution rate is crucial for improving therapeutic outcomes.
• Patients with swallowing difficulties require convenient and fast-acting dosage forms.

Purpose of the Study:

• To improve tolvaptan's solubility and dissolution rate through solid dispersion (SD) technology.
• To develop a fast-acting orally disintegrating tablet (ODT) formulation of tolvaptan.
• To enhance the overall efficacy and patient convenience of tolvaptan treatment.

Main Methods:

• Solid dispersions (SDs) were prepared using hydrophilic polymers, solubility enhancers, and complexing agents like hydroxypropyl-β-cyclodextrin (HPβCD).
• Formulations were characterized using solubility studies, X-ray diffraction, DSC, FTIR, SEM, and in vitro dissolution tests.
• Orally disintegrating tablets (ODTs) were formulated using the optimized SD formulation (HPβCD-SD2).

Main Results:

• The HPβCD-SD2 formulation demonstrated a significant increase in tolvaptan solubility (8.7-fold) compared to the pure drug.
• Over 90% of tolvaptan dissolved within 25 minutes from the HPβCD-SD2 formulation in various buffer solutions.
• The selected ODT formulation (code 59) exhibited excellent properties with friability ≤1% and disintegration time ≤180 seconds.

Conclusions:

• A novel SD formulation significantly enhanced tolvaptan's solubility and dissolution rate.
• The developed orally disintegrating tablets (ODTs) represent a viable alternative to existing tolvaptan products.
• This formulation improves drug delivery for patients, particularly those with swallowing impairments.