In situ monitoring of nanoparticle formation: Antisolvent precipitation of azole anti-fungal drugs

Kate P.M. McComiskey; Naila A. Mugheirbi; Jack Stapleton; Lidia Tajber

doi:10.1016/j.ijpharm.2018.03.054

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In situ monitoring of nanoparticle formation: Antisolvent precipitation of azole anti-fungal drugs

Journal article

Peer reviewed

In situ monitoring of nanoparticle formation: Antisolvent precipitation of azole anti-fungal drugs

Kate P.M. McComiskey, Naila A. Mugheirbi, Jack Stapleton and Lidia Tajber

International journal of pharmaceutics, Vol.543(1-2), pp.201-213

05/30/2018

DOI: 10.1016/j.ijpharm.2018.03.054

PMID: 29604371

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https://www.sciencedirect.com/science/article/pii/S0378517318302011?via%3DihubView

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Abstract

[Display omitted] In this work we report the effect of stabilizer choice and concentration on nanoparticle (NP) stability over time. Three different BCS class II active pharmaceutical ingredient (APIs): itraconazole (ITR), ketoconazole (KETO) and posaconazole (POS) were chosen due to their poor aqueous solubility and closely related chemical structures. Polyethylene glycol, polyethylene glycol methyl ether and polyethylene glycol dimethyl ether (DMPEG) with a molecular weight of 2000 Da were included as stabilisers. NPs were formed in situ using an anti-solvent addition, bottom up method at 25 °C. Colloidal stability was monitored using dynamic light scattering (DLS), accompanied by morphological examination of the NPs using scanning electron microscopy. Kinetic modelling indicates nanoparticle growth is driven by Ostwald ripening (OR). The presence of DMPEG causes OR growth to become an interface controlled process following a parabola trend. DMPEG encourages OR for POS NPs whilst driving the crystallisation process. The rate of OR appears to be inherent of the crystallisation pathway by which these APIs proceed. Crystallisation mechanisms are API, stabilizer type and concentration dependent. DLS is suitable as an initial systematic screening method for stabilizer selection, aiding the pharmaceutical scientist in the optimisation of nano-formulations.

Crystallisation

Dynamic light scattering

Itraconazole

Ketoconazole

Nanoparticle

Ostwald ripening

Posaconazole

Details

Title: Subtitle: In situ monitoring of nanoparticle formation: Antisolvent precipitation of azole anti-fungal drugs
Creators: Kate P.M. McComiskey - Trinity College Dublin
Naila A. Mugheirbi - Trinity College Dublin
Jack Stapleton - Trinity College Dublin
Lidia Tajber - Trinity College Dublin
Resource Type: Journal article
Publication Details: International journal of pharmaceutics, Vol.543(1-2), pp.201-213
DOI: 10.1016/j.ijpharm.2018.03.054
PMID: 29604371
NLM abbreviation: Int J Pharm
ISSN: 0378-5173
eISSN: 1873-3476
Publisher: Elsevier B.V
Grant note: name: Synthesis and Solid State Pharmaceutical Centre; DOI: 10.13039/501100001602, name: Science Foundation Ireland; DOI: 10.13039/501100008530, name: European Regional Development Fund, award: 12/RC/2275
Language: English
Date published: 05/30/2018
Academic Unit: Microbiology and Immunology; Infectious Diseases; Internal Medicine
Record Identifier: 9984297429602771

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