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Isolation of Itraconazole Nanostructured Microparticles via Spray Drying with Rational Selection of Optimum Base for Successful Reconstitution and Compaction


The addition of matrix formers within a formulation provides a means for enhancing the redispersibility of nanoparticles (NPs) enabling them to retain their advantageous properties imparted onto them by their sub-micron size. In this work, NPs were isolated in the solid state via spray drying with a range of sugars. The processed powders were characterized, establishing that itraconazole (ITR) nanostructured microparticles (NMPs) spray dried in the presence of mannitol and trehalose had favorable redispersibility confirmed by dynamic light scattering and nanoparticle tracking analysis. Solid-state analysis confirmed the crystalline nature of NMPs based on mannitol and the amorphous character of trehalose-based NMPs. The NMPs powders were compacted at a range of pressures, producing tablets with high tensile strength without compromising their disintegration time. A greater amount of ITR was solubilized from trehalose NMPs compared to the mannitol-based compacts in 0.1 M HCl, showing a promise for enhanced in vivo activity. Overall, as trehalose exhibited superior carrier properties for ITR NMPs, this type of excipient included in the formulation warrants careful consideration. The structured approach to matrix former selection and tabletting studies can reduce the amount of material and time required for testing in the initial stages of product development.

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Research leading to these results was supported by the Synthesis and Solid State Pharmaceutical Centre (SSPC), financed by a research grant from Science Foundation Ireland (SFI) and co-funded under the European Regional Development Fund (Grant Number 12/RC/2275). The authors would like to thank Mark Lynch for his help in the study.

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Correspondence to Lidia Tajber.

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McComiskey, K.P.M., McDonagh, A. & Tajber, L. Isolation of Itraconazole Nanostructured Microparticles via Spray Drying with Rational Selection of Optimum Base for Successful Reconstitution and Compaction. AAPS PharmSciTech 20, 217 (2019). https://doi.org/10.1208/s12249-019-1436-6

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  • itraconazole
  • nanoparticle
  • spray drying
  • solid state
  • tablets