Dissolution Rate Enhancement of Entacapone and Formulation of its Oro- Dispersible Tablets: Applying Statistical Design

Abstract:

The major aim of the study was to enhance the solubility and dissolution rate of entacapone by complexation with cyclodextrins (β-CD/HP β-CD). Further the selected cyclodextrin complexes are deigned to formulate oro-dispersible tablets (ODTs) using selected concentration of PEG 4000 as hydrophilic polymer and crospovidone as superdisintegrant. The phase solubility behavior of entacapone in presence of various concentrations of β-CD, HP β-CD, PEG 4000, PVP and Poloxamer 188 (0.25-5% w/v) was studied at 37 ± 2oC. Gibbs free energy (ΔG° tr) values in negative, indicates the spontaneous nature of entacapone solubilization. From dissolution rate studies it was observed β-CD complexes were better over HP β-CD and are formulated to ODTs by direct compression method. Response surface modeling approach (23 full factorial design) was used for design, development and data interpretation. The responses of the design were analyzed using Design Expert 8.0.7.1 (Stat-Ease Inc., USA). The optimized formulation was selected on the basis of software analysis with an overall desirability factor. The optimized formulation showed disintegration time of 40-42s, friability of 0.55% and a release of more than 85% within 45 m. The physicochemical characterizations of inclusion complexes and the optimized tablet formulation were done by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffraction (XRD).

Key words: Cyclodextrins, Entacapone, Inclusion complexation, Dissolution rate, Disintegration, 23 Factorial design.