Formulation and Evaluation of HPMC Phthalate Succinate-based Tablets of Tolvaptan: In vitro Evaluation

Aim: This study aimed to evaluate the performance of novel Hydroxy Propyl Methyl Cellulose Phthalate Succinate polymers (HPMCPS) as alternatives to Hydroxypropyl Methylcellulose Acetate Succinate (HPMCAS) and other polymers. Background: Tolvaptan, classified as a Biopharmaceutics Classification System (BCS) Class IV molecule, exhibits limited solubility and permeability, posing challenges for its formulation. Otsuka Pharmaceuticals addressed this by developing and patenting an amorphous solid dispersion using Hydroxypropyl Cellulose (HPC) as a carrier. In this study, a novel polymer, HPMCPS, was investigated with Tolvaptan as the model drug. Its in vitro performance was systematically compared to established polymers, including HPMCAS, to evaluate its potential as an alternative in enhancing drug solubility and delivery. Materials and Methods: Tolvaptan solid dispersions were prepared with Polyvinylpyrrolidone (PVP), HPC, Hydroxypropyl Methylcellulose (HPMC), HPMC succinate, HPMC phthalate, HPMCAS, and HPMCPS at the same drug-to-polymer ratio using the spray drying technique. Results and Conclusion: Tolvaptan and polymer Spray-Dried Solid Dispersions (SSD) were characterized by FTIR, DSC, SEM, and PXRD. Tablet formulations incorporating these SSDs were evaluated through in vitro dissolution and permeation studies. The shifting of peaks and reduction in peak intensities in FTIR spectroscopy indicated hydrogen bond interactions between the functional groups of the drug and the polymer. DSC studies showed higher glass transition temperatures and stability of SSDs. X-ray diffraction studies confirmed no evidence of crystalline form for all SSDs at the same polymer concentration, except for PVP 30, where some crystalline tolvaptan was observed, which in turn affected dissolution and release. Tolvaptan tablets prepared with novel polymer(s) (HPMCPS) solid dispersion demonstrated either the same or slightly faster dissolution and in vitro permeation behavior compared to the brand Tolvaptan tablets (Jinarc) and tablets prepared with HPC solid dispersion.