Comparison of physicochemical characteristics and stability ofthree nove! tormulationsot paclitaxel: Abraxane, Nanoxel, ana UenexolrMi-...
`
`rage 1o1Z
`
`AACR Meeting
`Abstracts Online
`
`HOME HELP FEEDBACK HOW TO CITE ABSTRACTS ARCHIVE CME INFORMATION SEARCH
`
`Cancer Research
`
`Clinical Cancer Research
`
`Molecular Cancer Therapeutics
`Cancer Epidemiology Biomarkers & Prevention
`Cancer Prevention Research
`Molecular Cancer Research
`Cancer Reviews Online
`Cancer Prevention Journals Portal
`Meeting Abstracts Online
`Annual Meeting Education Book
`Institution: INCYTE CORPORATION| Sign In via User Name/Password
`
`QUICK SEARCH:
`Author:
`Go| ron
`
`[advance
`Keyword(s):
`
`99th AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA
`
`This Article
`
`Drug Delivery and Targeting: Poster Presentations
`Proffered Abstracts
`Abstract #5622
`
`i Services |
`Similar articles in
`thi
`urnal
`Downloadto citation manager
`Google Scholar
`} Articles by Ron, N.
`Articles by Desai, N.
`
`Comparison of physicochemical
`characteristics and stability of three novel
`formulations of paclitaxel: Abraxane,
`Nanoxel, and Genexol PM
`
`PubMed
`galaeaiiarteiag We:
`
`Articles by Ron, N.
`
`Niles Ron, Jon Cordia, Andrew Yang, Sherry Ci, Phithi Nguyen, Melissa Hughs and Neil Desai
`
`Abraxis Bioscience, Inc., Los Angeles, CA
`
`Background: Abraxane (Abraxis BioScience, Inc., Los Angeles, CA, approved in USA and Canada),
`Nanoxel (Dabur Pharma, H.P., India, approved in India), and Genexol PM (Samyang Pharmaceuticals,
`Seoul, Korea, approved in Korea) are 3 commercially approved, novel formulations of paclitaxel.
`Abraxaneconsists of albumin-boundinjectable nanoparticles of paclitaxel, while Genexol and Nanoxel
`(utilizing cosolvents) are polymeric-micelle formulations. Abraxane and Genexolare lyophilized
`products approved for 25°C + 2°C storage, while Nanoxelis a liquid formulation approved for 2-8°C
`storage. This study investigated the physicochemical characteristics and short-term stability of the 3
`products under recommendedclinical use conditions and under accelerated conditions.
`Methods: The drugs were reconstituted and prepared per the instructions provided in the respective
`package inserts. Abraxane and Genexolwerereconstituted using the recommendedsaline diluent, while
`Nanoxel was mixed and diluted in 10% dextrose. Each drug was reconstituted to 0.7 mg/mL and 5
`mg/mL. Physical stability was monitored both visually and microscopically; particle size was measured
`and monitored over time at room temperature (RT, measured to be 23°C) and 40°C using photon
`correlation spectroscopy (PCS) (Zetasizer 3000, Malvern, UK). Chemical purity was measured by
`reduced reversed-phase HPLC (Shimadzu Scientific Instruments, MD).
`Results: Following reconstitution, Abraxane was determinedto be stable both physically and chemically
`
`Abraxis EX2022
`Actavis LLC v. Abraxis Bioscience, LLC
`IPR2017-01100
`
`

`

`Comparison ofphysicochemical characteristics andstability of three novel formulations ofpaclitaxel: Abraxane, Nanoxel, and Genexol PM-...
`
`Page 2 of 2
`
`at RT and 40°C over 24 hrs, with no evidence ofnanoparticle size growth at either 0.7 mg/mL or 5
`mg/mL. While reconstituted Genexol was stable at RT over 24 hrs, micelle instability resulting in
`precipitation of paclitaxel in the form of large needle-like crystals for both 0.7 mg/mL and 5 mg/mL
`formulations was seen between 2 to 4 hrs at 40°C. These observations were confirmed using orthogonal
`techniques, visual assessment from photomicrographs, and PCSparticle size measurement. For Nanoxel
`at 0.7 mg/mL, a minor, but consistent, increase in particle size was observed at RT over 24 hrs.
`However,significant aggregation, particle-size growth, and crystallization were seen within 4 hrs at 40°
`C. HPLC data comparing pre- and post-filtration confirmed that the crystal formation for both Nanoxel
`and Genexol resulted from paclitaxel precipitation and aggregation. In addition, analytical results
`showed that Nanoxelhad slightly lower paclitaxel purity as compared to either Abraxane or Genexol.
`Conclusions: Nanoparticle albumin-boundpaclitaxel, Abraxane, showed excellent physicochemical
`stability as compared to the micellar formulations, Nanoxel and Genexol. Particle size growth and
`crystal formation were readily apparent in Nanoxel and Genexol, especially in the short term under
`accelerated conditions.
`
`This Article
`
`Services
`Similar articles in this journal
`Download to citation manager
`
`Google Scholar
`
`W Articles b
`
`n, N.
`
`Articles by Desai, N.
`
`PubMed
`
`Articies by Ron, N.
`Articles by Desai, N.
`
`