Quality by design (QbD) approach to develop fast-dissolving tablets using melt-dispersion paired with surface-adsorption method: formulation and pharmacokinetics of flurbiprofen melt-dispersion granules.

Abstract

Developing amorphous solid dispersions with good flow properties is always challenging for formulation scientists to convert into tablets. Hence, the present study investigates the impact of the combination of melt-dispersion and surface-adsorption methods to prepare melt-dispersion granules with enhanced dissolution rate and flow properties. This study covers the formulation and pharmacokinetic study of fast-dissolving flurbiprofen tablets using PEG 6000 (hydrophilic carrier) and lactose (adsorbent). Response surface methodology (RSM) using the central composite design (CCD) was used to optimize independent variables like carrier concentrations and adsorbent concentrations, and their interactions with the dependent variables (responses), including solubility, angle of repose, Carr's index, and cumulative % drug release, were investigated. The optimized formulation was selected based on the numerical optimization method and further investigated for FTIR spectroscopy, differential scanning calorimetry, and X-ray diffractometry. Then, the optimized formulation was compressed into tablets and evaluated for both in vitro dissolution and in vivo pharmacokinetics parameters. In vitro dissolution studies revealed that the prepared fast-dissolving tablets released the drug entirely within 15min (Q15 of F4 tablets: 99.34 ± 1.24%), whereas conventional tablets took around 60min for complete dissolution. Pharmacokinetic studies in rats revealed that fast-dissolving tablets showed 1.38-fold higher peak-plasma concentration (Cmax) and 1.39-fold higher bioavailability than conventional tablets. Overall, this study revealed the successful fabrication of fast-dissolving tablets via melt-dispersion paired with the surface-adsorption method to enhance the flow properties and the dissolution rate.