Comparative physicochemical characterization of phospholipids complex of puerarin formulated by conventional and supercritical methods.
OBJECTIVE
The aim of this work was to compare the physicochemical characteristics of the phospholipids complex of puerarin (Pur) prepared by traditional methods (solvent evaporation, freeze-drying and micronization) and a supercritical fluid (SCF) technology. The physicochemical properties of the pure drug and the corresponding products prepared by two different SCF methods were also compared.


METHODS
Solid-state characterization of particles included differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), solubility, dissolution rate and scanning electron microscopy (SEM) examinations. Besides puerarin phospholipids complex (PPC) by four different methods, the solid-state properties of unprocessed, gas antisolvent (GAS) crystallized and solution enhanced dispersion by supercritical fluid (SEDS) precipitated puerarin samples were also compared. Crystallinity was assessed using DSC and XRPD. Drug-phospholipids interactions were characterized using Fourier transform infrared spectroscopy (FTIR). SEM was used to determine any morphological changes. Pharmaceutical performance was assessed in dissolution rate and solubility tests.


RESULTS
The results of the physical characterization attested a substantial correspondence of the solid state of the drug before and after treatment with GAS technique, whereas a pronounced change in size and morphology of the drug crystals was noticed. The GAS-processed puerarin exhibited a better crystal shape confirmed by DSC, XRPD and IR. Polymorphic change of puerarin during SEDS coupled with the dramatic reduction of the dimensions determined a remarkable enhancement of its solubility and in vitro dissolution rate. Phospholipids complex prepared using supercritical fluid technology showed similar properties of physical state, thermal stability and molecular interaction with phospholipids (PC) to those of corresponding systems prepared by other three conventional methods namely solvent evaporation, freeze-drying and micronization as proved by XRPD, DSC, and FTIR. The best dissolution rate was obtained by SEDS-prepared complex, while the highest solubility was obtained for solvent evaporation method.


CONCLUSIONS
Supercritical fluid technology for the preparation of puerarin and its phospholipids complex has been proven to have significant advantages over the solvent evaporation technique and other conventional methods.
Li
Ying
Y
Shanghai Jiao Tong University, Shanghai, PR China.
Yang
Da-Jian
DJ
Chen
Shi-Lin
SL
Chen
Si-Bao
SB
Chan
Albert Sun-Chi
AS
D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D025924:Chromatography, Supercritical Fluid; D018360:Crystallography, X-Ray; D000431:Ethanol / Q000737:chemistry; D005612:Freeze Drying; D007529:Isoflavones / Q000737:chemistry*; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D010743:Phospholipids / Q000737:chemistry*; D033362:Powder Diffraction; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods*; D014835:Volatilization