Evaluation of a crystalline nanosuspension: polymorphism, process induced transformation and in vivo studies.

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dc.contributor.author Sharma, P en
dc.contributor.author Zujovic, ZD en
dc.contributor.author Bowmaker, Graham en
dc.contributor.author Marshall, Andrew en
dc.contributor.author Denny, William en
dc.contributor.author Garg, Sanjay en
dc.coverage.spatial Netherlands en
dc.date.accessioned 2011-11-17T17:20:31Z en
dc.date.issued 2011-04-15 en
dc.identifier.citation International Journal of Pharmaceutics 408(1-2):138-151 15 Apr 2011 en
dc.identifier.issn 0378-5173 en
dc.identifier.uri http://hdl.handle.net/2292/9237 en
dc.description.abstract The aim of this work was to evaluate a crystalline nanosuspension of an investigational anticancer compound, SN 30191. Solid forms of SN 30191 were prepared and characterized by thermal analysis, infrared spectroscopy, ¹³C CP/MAS SSNMR spectroscopy, SEM and powder XRD. Wet milling was performed using a high pressure homogenizer and process induced transformations were studied as a function of time and pressure using infrared spectroscopy. Dose-toxicity and pharmacokinetics (PK) of the nanocrystal formulation were evaluated in mice after intravenous administration. SN 30191 was found to exist in two polymorphic forms (I and II) and a hydrate with an equilibrium solubility < 0.1 μg/ml (pH 1.3-11.0, 37 °C). Wet milling resulted in solid state transformation as a function of pressure. Form II was found to transform into form I at intermediate pressures. A further increase in pressure resulted in formation of a hydrate. The final nanosuspension consisted of SN 30191 as a hydrate. The dose-toxicity studies revealed higher tolerance (~4 times) for the nanosuspension (10 mg/kg) when compared with a solution formulation (2.5 mg/kg). Compared with solution formulation, the nanosuspension allowed the delivery of a higher dose and rendered possible the performance of PK and tissue distribution studies in animals. en
dc.language eng en
dc.publisher Elsevier B.V. en
dc.relation.ispartofseries International Journal of Pharmaceutics en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from http://www.sherpa.ac.uk/romeo/issn/0378-5173/ en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.subject Animals en
dc.subject Antineoplastic Agents en
dc.subject Chemistry, Pharmaceutical en
dc.subject Crystallization en
dc.subject Differential Thermal Analysis en
dc.subject Dose-Response Relationship, Drug en
dc.subject Drug Carriers en
dc.subject Drug Stability en
dc.subject Injections, Intravenous en
dc.subject Male en
dc.subject Mice en
dc.subject Mice, Inbred C57BL en
dc.subject Microscopy, Electron, Scanning en
dc.subject Molecular Structure en
dc.subject Nanoparticles en
dc.subject Phase Transition en
dc.subject Pyrimidinones en
dc.subject Solubility en
dc.subject Spectrophotometry, Infrared en
dc.subject Suspensions en
dc.subject Tissue Distribution en
dc.title Evaluation of a crystalline nanosuspension: polymorphism, process induced transformation and in vivo studies. en
dc.type Journal Article en
dc.identifier.doi 10.1016/j.ijpharm.2011.01.032 en
pubs.issue 1-2 en
pubs.begin-page 138 en
pubs.volume 408 en
dc.rights.holder Copyright: Elsevier B.V. en
dc.identifier.pmid 21272627 en
pubs.end-page 151 en
dc.rights.accessrights http://purl.org/eprint/accessRights/RestrictedAccess en
pubs.subtype Article en
pubs.elements-id 202983 en
pubs.org-id Medical and Health Sciences en
pubs.org-id Medical Sciences en
pubs.org-id Auckland Cancer Research en
pubs.org-id Science en
pubs.org-id Chemistry en
pubs.org-id Science Research en
pubs.org-id Maurice Wilkins Centre (2010-2014) en
dc.identifier.eissn 1873-3476 en
dc.identifier.pii S0378-5173(11)00063-9 en
pubs.record-created-at-source-date 2011-11-17 en
pubs.dimensions-id 21272627 en

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