Improvement of physicochemical and biopharmaceutical properties of flurbiprofen using melt sonocrystallization technique

Abstract

AbstractThe aim of the present study was to investigate the suitability of the melt sonocrystallization technique to modify the undesirable properties of the nonsteroidal anti‐inflammatory drug (NSAID), flurbiprofen (FBP), e.g., poor flowability, solubility, and dissolution rate and, consequently, poor bioavailability. FBP melt was poured in deionized water at 25°C and sonicated for 4 min at an amplitude of 60% and cycle of 40 s on and 10 s off. The product obtained was evaluated using scanning electron microscopy (SEM), image analysis, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT‐IR), and X‐ray powder diffraction (XRPD). Flow properties, intrinsic dissolution rate, solubility, and bioavailability were also evaluated. The particle size of the treated FBP was significantly reduced. Thermal behavior and FT‐IR spectra of untreated and treated FBP have shown no significant difference. Low‐intensity peaks in the X‐ray diffraction of treated FBP were noticed. In addition there was significant enhancement in the flow properties of treated FBP, as indicated by the value of angle of repose and the flow constants calculated from the Kawakita equation. The increased solubility of treated FBP was about 35%. The intrinsic dissolution rate of treated FBP increased by 2‐fold. The dissolution rate studies revealed that 90% of the drug was released within 20 min for treated FBP compared with 60% released for the untreated drug. The relative bioavailability of treated FBP was increased by 2‐fold compared with untreated drug.The use of melt sonocrystallization technique is a promising technique that may afford powder with improved flow and tablet functionality as well as improved dissolution and bioavailability. Drug Dev Res 69:34–41, 2008 © 2008 Wiley‐Liss, Inc.