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

Area of Science:

• Pharmaceutical Technology
• Materials Science

Background:

• Ibuprofen (IBF) often requires particle size reduction to improve its therapeutic efficacy.
• Enhancing drug solubility and dissolution is crucial for effective oral drug delivery.

Purpose of the Study:

• To systematically produce ibuprofen particles with leucine using wet milling.
• To investigate the impact of wet milling and leucine on ibuprofen particle size, solubility, and dissolution.

Main Methods:

• Ibuprofen particles were produced via high shear wet milling.
• Particle size, morphology, thermal properties, and chemical interactions were characterized using Mastersizer, SEM, DSC, XRD, ATR-FTIR, and TGA.
• Solubility and in-vitro dissolution were assessed using HPLC in phosphate buffer solution.

Main Results:

• Wet milling reduced ibuprofen particle size from 71.3 μm to 1.7 μm.
• Micronized ibuprofen with leucine exhibited increased saturation solubility (168.7 µg/mL) compared to original ibuprofen (147.4 µg/mL).
• Ibuprofen particles with 2.5-6.25% leucine showed 100% drug release, significantly higher than original particles (55.9%).

Conclusions:

• Wet milling is an efficient technique for ibuprofen particle size reduction.
• Leucine incorporation significantly enhances ibuprofen solubility and dissolution, likely through hydrogen bonding.
• The developed method offers a robust approach for manufacturing drug particles with improved bioavailability.