Super-fast production of drug nanocrystals: Dual asymmetric centrifugation-enabled media milling applied to high throughput formulation screening
Drug nanocrystals (NCs) have entirely changed the panorama of drug delivery, enabling enhanced drug absorption and long-acting drug release. The vast majority of marketed NCs-based products are obtained via media milling using of-the-shelf industrial machinery. However, early-stage formulation devel...
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| Language: | English |
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Elsevier
2025-07-01
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| Series: | Materials & Design |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0264127525006367 |
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| author | Lucia Lopez-Vidal Maria G. Bordon Alejandro J. Paredes |
| author_facet | Lucia Lopez-Vidal Maria G. Bordon Alejandro J. Paredes |
| author_sort | Lucia Lopez-Vidal |
| collection | DOAJ |
| description | Drug nanocrystals (NCs) have entirely changed the panorama of drug delivery, enabling enhanced drug absorption and long-acting drug release. The vast majority of marketed NCs-based products are obtained via media milling using of-the-shelf industrial machinery. However, early-stage formulation development is time-consuming and challenging when limited active amounts are available. This study demonstrates the feasibility of producing NCs using dual asymmetric centrifugation (DAC) in a single 1-minute milling cycle. The methodology proved effective for 9 out of 10 evaluated drugs, achieving particle sizes as low as 174 nm. Subsequently, three drugs were selected for an in-depth study of the influence of various parameters on particle size and polydispersity index (PDI). The crystallinity and morphology of the resulting NCs were investigated using thermal analysis and transmission electron microscopy. Potential sample contamination was assessed using nanoparticle tracking analysis, with values < 1 %. A multiple-response optimization study and a microhydrodynamic analysis of the milling established a quantitative relationship between the process variables and particle size. Furthermore, it established that the DAC methodology significantly outperforms conventional laboratory-scale wet media milling in terms of milling efficiency. The findings of this study position DAC as a rapid, cost-effective, and efficient top-down wet media milling method to obtain NCs. |
| format | Article |
| id | doaj-art-1783f46db7d34ef690ed9bb9712d8a30 |
| institution | Kabale University |
| issn | 0264-1275 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials & Design |
| spelling | doaj-art-1783f46db7d34ef690ed9bb9712d8a302025-08-20T03:30:43ZengElsevierMaterials & Design0264-12752025-07-0125511421610.1016/j.matdes.2025.114216Super-fast production of drug nanocrystals: Dual asymmetric centrifugation-enabled media milling applied to high throughput formulation screeningLucia Lopez-Vidal0Maria G. Bordon1Alejandro J. Paredes2School of Pharmacy, Queen’s University Belfast, Medical Biology Centre, 97 Lisburn Road, BT9 7BL Northern Ireland, United KingdomInstituto de Ciencia y Tecnología de Alimentos Córdoba (ICYTAC-CONICET, UNC), Córdoba, ArgentinaSchool of Pharmacy, Queen’s University Belfast, Medical Biology Centre, 97 Lisburn Road, BT9 7BL Northern Ireland, United Kingdom; Corresponding author at: Senior Lecturer in Pharmaceutical Sciences, School of Pharmacy, Queens University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast, BT9 7BL, Northern Ireland, United Kingdom.Drug nanocrystals (NCs) have entirely changed the panorama of drug delivery, enabling enhanced drug absorption and long-acting drug release. The vast majority of marketed NCs-based products are obtained via media milling using of-the-shelf industrial machinery. However, early-stage formulation development is time-consuming and challenging when limited active amounts are available. This study demonstrates the feasibility of producing NCs using dual asymmetric centrifugation (DAC) in a single 1-minute milling cycle. The methodology proved effective for 9 out of 10 evaluated drugs, achieving particle sizes as low as 174 nm. Subsequently, three drugs were selected for an in-depth study of the influence of various parameters on particle size and polydispersity index (PDI). The crystallinity and morphology of the resulting NCs were investigated using thermal analysis and transmission electron microscopy. Potential sample contamination was assessed using nanoparticle tracking analysis, with values < 1 %. A multiple-response optimization study and a microhydrodynamic analysis of the milling established a quantitative relationship between the process variables and particle size. Furthermore, it established that the DAC methodology significantly outperforms conventional laboratory-scale wet media milling in terms of milling efficiency. The findings of this study position DAC as a rapid, cost-effective, and efficient top-down wet media milling method to obtain NCs.http://www.sciencedirect.com/science/article/pii/S0264127525006367Wet media millingTop-downNanoparticlesNanosuspensionsCurcuminAlbendazole |
| spellingShingle | Lucia Lopez-Vidal Maria G. Bordon Alejandro J. Paredes Super-fast production of drug nanocrystals: Dual asymmetric centrifugation-enabled media milling applied to high throughput formulation screening Materials & Design Wet media milling Top-down Nanoparticles Nanosuspensions Curcumin Albendazole |
| title | Super-fast production of drug nanocrystals: Dual asymmetric centrifugation-enabled media milling applied to high throughput formulation screening |
| title_full | Super-fast production of drug nanocrystals: Dual asymmetric centrifugation-enabled media milling applied to high throughput formulation screening |
| title_fullStr | Super-fast production of drug nanocrystals: Dual asymmetric centrifugation-enabled media milling applied to high throughput formulation screening |
| title_full_unstemmed | Super-fast production of drug nanocrystals: Dual asymmetric centrifugation-enabled media milling applied to high throughput formulation screening |
| title_short | Super-fast production of drug nanocrystals: Dual asymmetric centrifugation-enabled media milling applied to high throughput formulation screening |
| title_sort | super fast production of drug nanocrystals dual asymmetric centrifugation enabled media milling applied to high throughput formulation screening |
| topic | Wet media milling Top-down Nanoparticles Nanosuspensions Curcumin Albendazole |
| url | http://www.sciencedirect.com/science/article/pii/S0264127525006367 |
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