A novel temperature-controlled media milling device to produce drug nanocrystals at the laboratory scale.

Autor: Catlin EJ; School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK., Fandiño OE; School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK., Lopez-Vidal L; School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK; Faculty of Chemical Sciences, National University of Córdoba (FCQ-UNC), Haya de la Torre y Medina Allende, X5000XHUA, Córdoba, Argentina., Sangalli M; School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK., Donnelly RF; School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK., Palma SD; Faculty of Chemical Sciences, National University of Córdoba (FCQ-UNC), Haya de la Torre y Medina Allende, X5000XHUA, Córdoba, Argentina., Paredes AJ; School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK. Electronic address: a.paredes@qub.ac.uk.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2024 Sep 28; Vol. 666, pp. 124780. Date of Electronic Publication: 2024 Sep 28.
DOI: 10.1016/j.ijpharm.2024.124780
Abstrakt: Poor aqueous solubility of preexisting and emerging drug molecules is a common issue faced in the field of pharmaceutics. To address this, particle size reduction techniques, including drug micro- and nanonisation have been widely employed. Nanocrystals (NCs), drug particles with particle sizes below 1 µm, offer high drug content, improved dissolution, and long-acting capabilities. Media milling is the most used method to prepare NCs using of-the-shelf machinery, both at the laboratory and industrial scales. However, early NCs development, especially when limited amounts of the active are available, require the use of milligram-scale media milling. This study introduces a novel mini-scale milling device (Mini-mill) that incorporates temperature control through a water-cooled jacket. The device was used to produce NCs of three model hydrophobic drugs, itraconazole, ivermectin and curcumin, with lowest particle sizes of 162.5 ± 0.4 nm, 178 ± 2 nm, and 116.7 ± 0.7 nm, respectively. Precise control of milling temperature was achieved at 15, 45, and 75°C, with drug dependent particle size reduction trends, with no adverse effects on the milling materials or polymorphic changes in the NCs, as confirmed by calorimetric analysis. Finally, a scale-up feasibility study was carried out in a lab-scale NanoDisp®, confirming that the novel Mini-mills are a material-efficient tool for early formulation development, with potential for scale-up to commercial mills.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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