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Robust Wet Milling Technique for Producing Micronized Ibuprofen Particles with Improved Solubility and Dissolution

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Abstract

This study investigated a systematic approach for producing ibuprofen (IBF) particles with leucine by wet milling. Using a high shear homogenizer, the particles size of the IBF was reduced. Prepared IBF microparticles were freeze-dried and characterized by using Mastersizer, SEM, DSC, XRD, ATR-FTIR, and TGA. The drug saturation solubility and in-vitro dissolution performance were carried out in phosphate buffer solution (PBS, pH 7.4) at 37°C temperature and IBF were determined using a validated HPLC method. The wet-milled method reduced the particle size from 71.3 to 1.7 μm. The minimum particle size of IBF was obtained in 0.05% Tween 80 solution homogenized at 17,000 rpm for 15 min. The saturated solubility (168.7 µg/mL) of the micronized IBF particles with leucine showed higher compared to that of the original IBF (147.4 µg/mL) in PBS solution. The prepared IBF particles containing 2.5–6.25% leucine showed significantly higher IBF release (100%) compared to that of original drug particles (55.9%) in 120 min. The excipient leucine played a major role in enhancing the solubility and dissolution profile of the prepared IBF particles probably by the formation of hydrogen bonding. The developed wet milling was an efficient and robust technique for reducing the particle size of IBF and could be a useful method for manufacturing drug particles with enhanced solubility and dissolution.

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Abbreviations

IBF:

ibuprofen

L-leucine:

Leucine

ATR-FTIR:

Attenuated total reflectance-Fourier transform infrared

DSC-:

Differential scanning calorimetry

TGA:

Thermogravimetric analysis

SEM:

Scanning electron microscopy

XRPD:

X-ray powder diffraction

USP:

United States Pharmacopoeia

HPLC:

High-performance liquid chromatography

%:

Percent

µg:

Microgram

µm:

Micrometer

°C:

Degree Celsius

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Acknowledgements

The authors would like to thank Queensland University of Technology (QUT) for providing all laboratory facilities, and scientific and technical supports to complete this project. We are more grateful to the Central Analytical Research Facility (CARF) hosted by the Institute for Future Environments (IFE) at QUT.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Pharmacy Discipline, School of Clinical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia

    Shahjabeen Sharif & Nazrul Islam

  2. School of Chemistry and Physics, Science and Engineering Faculty, Queensland University of Technology, Brisbane, QLD, Australia

    Saiqa Muneer & Emad L. Izake

  3. Central Analytical Research Facility, Institution for Future Environment, Queensland University of Technology, Brisbane, QLD, Australia

    Tony Wang

  4. Centre for Immunology and Infection Control (CIIC), Queensland University of Technology, Brisbane, QLD, Australia

    Nazrul Islam

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  1. Shahjabeen Sharif
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Contributions

The authors of this study and the manuscript text contributed as follows:

Shahjabeen Sharif – writing original draft, methodology, investigation, data curation, validation.

Saiqa Muneer – SEM analysis, visualization, data curation.

Tony Wang – investigating XRD analysis, validation, data curation.

Emad L. Izake – supervision, conceptualization.

Nazrul Islam – Supervision, project administration, conceptualization, resources, methodology, writing- review, feedbacking, and editing.

Corresponding author

Correspondence to Nazrul Islam.

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The authors declare no competing interests.

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Sharif, S., Muneer, S., Wang, T. et al. Robust Wet Milling Technique for Producing Micronized Ibuprofen Particles with Improved Solubility and Dissolution. AAPS PharmSciTech 24, 16 (2023). https://doi.org/10.1208/s12249-022-02480-w

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