Formulation optimization of orally disintegrating tablets containing solid dispersion of felodipine and hydroxypropyl methylcellulose using face-centered central composite design

A novel dosage form integrating solid dispersion (SD) in orally disintegrating tablets (ODTs) was developed and optimized by the face-centered central composite design to improve poorly soluble property and slow onset action time of felodipine (Fel). SD of Fel and hydroxypropyl methylcellulose E6 was prepared by solvent evaporation method. Differential scanning calorimetry and fourier transforms infrared spectroscopy indicated that Fel transformed from crystalline to amorphous state by the formation of hydrogen bond between –N–H in Fel and O–R in HPMC. The accelerated stability test in 45 °C, 75 % RH demonstrated that the optimized SD was stable in terms of the dissolution rate of Fel and thermodynamic property. The ODTs containing SD (Fel:HPMC E6 = 1:3) were prepared by direct compression technique. The face-centered central composite design with the ODT-SD was employed to investigate the effect of mannitol (X 1 ), crospovidone XL (X 2 ) on the ODT-SD disintegration time (Y 1 ), % Fel released after 5 min (Y 2 ) and the ODT-SD friability (Y 3 ). ANOVA test showed that X 2 and X 2 * X 2 had a significant effect on the ODT-SD disintegration time ( p 0.05). The ODT-SD friability was substantially proportional to the amount of mannitol (X 1 ) ( p