The preparation and characterization of sorafenib solid dispersion

SHAN Xingjie; YAN Zhankuan; YU Chaofeng; LI Chuanjun

doi:10.3969/j.issn.1006-0111.2016.04.009

Message Board

Respected readers, authors and reviewers, you can add comments to this page on any questions about the contribution, review, editing and publication of this journal. We will give you an answer as soon as possible. Thank you for your support!

Name

E-mail

Phone

Title

Content

Verification Code

Objective To prepare sorafenib (SFN)/mesoporous silica solid dispersion (SD) and investigate characteristics in vitro and in vivo. Methods The SD was prepared by solvent evaporation method; the optimal ratio of SFN to mesoporous silica was determined by examining the dissolution of formula, the drug state and physical stability of SD were examined by DSC and XRD; the surface morphology was characterized by electron microscope; the pharmacokinetics of SD was studied for the solid dispersion which compared with SFN powders in vivo study using rats. Results SFN raw drug was crystalline and its dissolution was <10%; the dissolution of SD increased with an increase in amount of mesoporous silica; when the ratio of SFN to mesoporous silica was 1:5, drug in SD was non-crystalline state and the dissolution was >90%. The physical state and dissolution of SFN in SD were hardly changed during the six months accelerated test. The c_max of SD group was 1.8 times that of powder group, relative bioavailability was 175%. Conclusion The physical stability of self-preparing solid dispersions is good, the dissolution and oral absorption are improved by solid dispersion.

The preparation and characterization of sorafenib solid dispersion

Jiang Su Heng Rui Medicine Co., Ltd., Lianyungang 222047, China

Received Date: 2015-09-09

Rev Recd Date: 2016-01-14

Key words:

Abstract: Objective To prepare sorafenib (SFN)/mesoporous silica solid dispersion (SD) and investigate characteristics in vitro and in vivo. Methods The SD was prepared by solvent evaporation method; the optimal ratio of SFN to mesoporous silica was determined by examining the dissolution of formula, the drug state and physical stability of SD were examined by DSC and XRD; the surface morphology was characterized by electron microscope; the pharmacokinetics of SD was studied for the solid dispersion which compared with SFN powders in vivo study using rats. Results SFN raw drug was crystalline and its dissolution was <10%; the dissolution of SD increased with an increase in amount of mesoporous silica; when the ratio of SFN to mesoporous silica was 1:5, drug in SD was non-crystalline state and the dissolution was >90%. The physical state and dissolution of SFN in SD were hardly changed during the six months accelerated test. The c_max of SD group was 1.8 times that of powder group, relative bioavailability was 175%. Conclusion The physical stability of self-preparing solid dispersions is good, the dissolution and oral absorption are improved by solid dispersion.

HTML

Reference (12)

[1]	Liu L, Cao Y, Chen C, et al. Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5[J]. Cancer Res, 2006, 66(24):11851-11858.
[2]	Furuse J. Sorafenib for the treatment of unresectable hepatocellular carcinoma[J]. Biologics, 2008, 12(4):779-788.
[3]	Wang XQ, Fan JM, Liu YO et al. Bioavailability and pharmacokinetics of sorafenib suspension, nanoparticles and nanomatrix for oral administration to rat[J]. Int J Pharm, 2011, 419(1-2):339-346.
[4]	Kim MS. Soluplus-coated colloidal silica nanomatrix system for enhanced supersaturation and oral absorption of poorly water-soluble drugs[J]. Artif Cells Nanomed Biotechnol, 2013, 41(6):363-367.
[5]	Wang L, Cui FD, Sunada H. Preparation and evaluation of solid dispersions of nitrendipine prepared with fine silica particles using the melt-mixing method[J]. Chem Pharm Bull, 2006, 54(1):37-43.
[6]	Charnay C, Bégu S, Tourné-Péteilh C, et al. Inclusion of ibuprofen in mesoporous templated silica:drug loading and release property[J]. Eur J Pharm Biopharm. 2004, 57(3):533-540.
[7]	Gupta P, Chawla G, Bansal AK. Physical stability and solubility advantage from amorphous celecoxib:the role of thermodynamic quantities and molecular mobility[J]. Mol Pharm, 2004, 1(6):406-413.
[8]	Salonen J, Laitinen L, Kaukonen AM, et al. Mesoporous silicon microparticles for oral drug delivery:loading and release of five model drugs[J]. J Control Release, 2005, 108(2-3):362-374.
[9]	Blanchet B, Billemont B, Cramard J, et al. Validation of an HPLC-UV method for sorafenib determination in human plasma and application to cancer patients in routine clinical practice[J]. J Pharm Biomed Anal, 2009, 49(4):1109-1114.
[10]	Wang XQ, Dai JD, Zhang H, et al. Absorption mechanism of cyclosporine A loaded pH-sensitive nanoparticles in rats[J]. J Nanosci Nanotechnol, 2008, 8(5):2422-2431.
[11]	Miller DA, Di Nunzio JC, Yang W, et al. Targeted intestinal delivery of supersaturated itraconazole for improved oral absorption[J]. Pharm Res, 2008, 25(6), 1450-1459.
[12]	Janssens S, De Zeure A, Paudel A, et al. Influence of preparation methods on solid state supersaturation of amorphous solid dispersions:a case study with itraconazole and Eudragit E100[J]. Pharm Res, 2010, 27(5), 775-785.

Message Board

The preparation and characterization of sorafenib solid dispersion

doi: 10.3969/j.issn.1006-0111.2016.04.009

Abstract

References

Proportional views

通讯作者: 陈斌, [email protected]

Article Metrics

Related

Proportional views