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Comparative Physicochemical Characterization of Phospholipids Complex of Puerarin Formulated by Conventional and Supercritical Methods

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Abstract

Purpose

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.

Result

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.

Conclusion

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.

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Abbreviations

Co:

drug concentration in medium

Cs:

saturated concentration in the diffused layer

D:

diffusion coefficient

DSC:

differential scanning calorimetry

EC:

ethyl cellulose

FD-PPC:

puerarin phospholipids complex prepared by freeze-drying method

FTIR:

Fourier transform infrared spectroscopy

GAS:

gas antisolvent

GAS-PC:

phospholipids prepared by GAS method

GAS-Pur:

puerarin prepared by GAS method

H:

diffusion layer thickness

MPPC:

puerarin phospholipids complex prepared by micronization method

PC:

phospholipids

PEG:

poly ethylene glycol

PLA:

poly lactic acid

PM:

physical mixture of puerarin and phospholipids

PPC:

puerarin phospholipids complex

Pur:

puerarin

PVP:

polyvinyl pyrrolidone

RESS:

rapid expansion of supercritical solution

S:

surface area

SAS:

supercritical antisolvent precipitation

SC-CO2 :

supercritical CO2

SCF:

supercritical fluid

SEDS:

solution enhanced dispersion by supercritical fluid

SEM:

scanning electron microscopy

SEDS-PC:

phospholipids prepared by SEDS method

SEDS-PPC:

puerarin phospholipids complex prepared by SEDS method

SEDS-Pur:

puerarin prepared by SEDS method

SE-PPC:

puerarin phospholipids complex prepared by solvent evaporation method

UV:

ultra violet

V:

medium volume

XRPD:

X-ray powder diffraction

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Authors and Affiliations

  1. Shanghai Jiao Tong University, Shanghai, PR China

    Ying Li

  2. Shenzhen Virtual University Park Postdoc Station, Shenzhen, PR China

    Ying Li

  3. State Key Laboratory of Chinese Medicine and Molecular Pharmacology, 6/F, Block R2-A, Southern Area of the Shenzhen Hi-Tech Park Nanshan District, Shenzhen, PR China

    Ying Li, Da-Jian Yang, Shi-Lin Chen, Si-Bao Chen & Albert Sun-Chi Chan

  4. Institute of Medicinal Plant Development, Chinese Academy of Medical College, Beijing, PR China

    Shi-Lin Chen & Si-Bao Chen

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  1. Ying Li
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  2. Da-Jian Yang
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Li, Y., Yang, DJ., Chen, SL. et al. Comparative Physicochemical Characterization of Phospholipids Complex of Puerarin Formulated by Conventional and Supercritical Methods. Pharm Res 25, 563–577 (2008). https://doi.org/10.1007/s11095-007-9418-x

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  • DOI: https://doi.org/10.1007/s11095-007-9418-x

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