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Heat induced evaporative antisolvent nanoprecipitation (HIEAN) of itraconazole
Mugheirbi, N.A. Paluch, Krzysztof J. Tajber, L.
Mugheirbi, N.A.
Paluch, Krzysztof J.
Tajber, L.
Publication Date
2014-08
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© 2014 Elsevier. Reproduced in accordance with the publisher's selfarchiving
policy. This manuscript version is made available under the CC-BY-NC-ND 4.0 license.
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openAccess
Accepted for publication
2014-05-26
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Abstract
Itraconazole (ITR) is an antifungal drug with a limited bioavailability due to its poor aqueous
solubility. In this study, ITR was used to investigate the impact of nanonisation and solid state
change on drug’s apparent solubility and dissolution. A bottom up approach to the production
of amorphous ITR nanoparticles (NPs), composed of 100% drug, with a particle diameter below
250 nm, using heat induced evaporative antisolvent nanoprecipitation (HIEAN) from acetone
was developed. The NPs demonstrated improved solubility and dissolution in simulated gastrointestinal
conditions when compared to amorphous ITR microparticles. NPs produced with
polyethylene glycol (PEG) or its methoxylated derivative (MPEG) as a stabiliser enabled the
production of smaller NPs with narrower particle size distribution and enhanced apparent
solubility. MPEG stabilised NPs gave the greatest ITR supersaturation levels (up to 11.6 ± 0.5
μg/ml) in simulated gastric fluids. The stabilising polymer was in an amorphous state. Dynamic
vapour sorption data indicated no solid state changes in NP samples with water vapour at 25 °C,
while crystallisation was apparent at 50 °C. HIEAN proved to be an efficient method of
production of amorphous ITR NPs, with or without addition of a polymeric stabiliser, with
enhanced pharmaceutical properties.
Version
Accepted manuscript
Citation
Mugheirbi NA, Paluch KJ and Tajber L (2014) Heat induced evaporate antisolvent
nanoprecipitation (HIEAN) of itraconazole. International Journal of Pharmaceutics. 471(1-2): 400-
411.
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Article