Physicochemical stability, pharmacokinetic, and biodistribution evaluation of paclitaxel solid dispersion prepared using supercritical antisolvent process

Title
Physicochemical stability, pharmacokinetic, and biodistribution evaluation of paclitaxel solid dispersion prepared using supercritical antisolvent process
Author(s)
용철순스리니바산 샨무간[스리니바산 샨무간]박재현한미약품[박재현한미약품]지상철[지상철]최한곤[최한곤]우종수[우종수]
Keywords
CREMOPHOR-EL; INDOMETHACIN CRYSTALLIZATION; NONLINEAR PHARMACOKINETICS; MOLECULAR DISPERSIONS; MULTIDRUG-RESISTANCE; LIPID NANOPARTICLES; CONTROLLED DELIVERY; BRAIN-TUMORS; TAXOL; DRUG
Issue Date
201103
Publisher
INFORMA HEALTHCARE
Citation
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY, v.37, no.6, pp.628 - 637
Abstract
Aim: To investigate the physicochemical stability, pharmacokinetics (PK), and biodistribution of paclitaxel (PTX) from paclitaxel solid dispersion (PSD) prepared by supercritical antisolvent (SAS) process. Methods: Physicochemical stability was performed in accelerated (40 degrees C 70 +/- 5% RH) and stress (60 degrees C) storage conditions for a period of 6 months and 4 weeks, respectively. PK and biodistribution studies were performed in rats following i.v. administration of PTX equivalent to 6 and 12 mg/kg formulations. Results: Physical stability of PSD showed excellent stability with no recrystallization of the amorphous form. Chemical stability of PSD in terms of % PTX remaining was 98.2 +/- 0.6% at 6 months and 97.9 +/- 0.3% at 4 weeks of accelerated and stress conditions, respectively. The PK study showed a nonlinear increase in AUC with increasing dose, that is, 100% increase in dose (from 6 to 12 mg/kg) resulted in 405.90% increase in AUC. Unlike PK study, the organ distribution study of PTX from PSD showed linear relationship with dose escalation. The order of organ distribution of PTX from highest to lowest for both PSD and Taxol (R) was liver>kidney>lung>brain. Conclusions: This study demonstrated excellent physicochemical stability with insight information on the PK and biodistribution of PTX from PSD prepared by SAS process.
URI
http://hdl.handle.net/YU.REPOSITORY/25505http://dx.doi.org/10.3109/03639045.2010.533682
ISSN
0363-9045
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약학대학 > 약학부 > Articles
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