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Micronization of a Soft Material: Air-Jet and Micro-Ball Milling

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Abstract

The air-jet and ball-mill are frequently used in fine micronization of active pharmaceutical ingredients to the order of 1–5 μm, which is important for increasing dissolution rates, and also for pulmonary delivery. In this study, we investigated the ability of air-jet and ball-mill to achieve adequate micronization on the lab scale using a model soft material, Pluronic® F-68. Material mechanical properties were characterized using the nanometer 600. Pluronic® F-68 was ball-milled in a micro-mill at different material weights and durations in liquid nitrogen vapor. In comparison, a lab scale air-jet mill was used at various milling parameters according to a full factorial design, where the response factors were particle yield and particle size distribution, which was analyzed using laser diffraction and scanning electron microscopy. The yield achieved with the micro-ball mill was 100% but was ~80% for the air-jet mill, which reduced the size of Pluronic® F-68 from 70 μm to sizes ranging between 23–39 μm median diameters. Ball milling produced particles less than 10 μm after 15 min. Although air-jet milling proved capable of particle size reduction of the relatively soft material Pluronic® F-68, limitations to the lower size range achievable were observed. The feed rate of the material into the air jet mill was a significant factor and slower feed rates lead to smaller sizes by allowing more time for particle collisions and subsequent particle breakage to occur. Micro-ball milling under cold condition was more successful at achieving a lower range particle size reduction of soft materials.

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Acknowledgments

The authors would like to acknowledge that a portion of this work was performed by them when working at the College of Pharmacy, University of New Mexico, USA. The authors would also like to thank Dr Marwan Al-Haik at Department of Mechanical Engineering, School of Engineering, University of New Mexico, USA, for his help in using the nanotester 600 and determining the results.

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Authors and Affiliations

  1. School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, L3 3AF, UK

    Imran Y. Saleem

  2. College of Pharmacy, University of Texas at Austin, Austin, Texas, 78712, USA

    Hugh D. C. Smyth

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  1. Imran Y. Saleem
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  2. Hugh D. C. Smyth
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Correspondence to Imran Y. Saleem.

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Saleem, I.Y., Smyth, H.D.C. Micronization of a Soft Material: Air-Jet and Micro-Ball Milling. AAPS PharmSciTech 11, 1642–1649 (2010). https://doi.org/10.1208/s12249-010-9542-5

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  • DOI: https://doi.org/10.1208/s12249-010-9542-5

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