(397c) Mitigating Electrostatic Chargeability of Ibuprofen by Wet Co-Milling with Polyvinylpyrrolidone

Milling, also known as comminution or grinding, is typically regarded as a particle size reduction process across many industries, including the manufacturing of pharmaceuticals and fine chemicals. In secondary pharmaceutical processing, milling is often used to increase the specific surface area of poorly water-soluble drugs, so as to improve their dissolution properties and bioavailability.  However, besides reducing the particle size, the milling process is often accompanied by other unintended effects such as electrostatic charging.  During the milling process, the contact between particles rubbing against each other and with the vessel wall causes undesirable triboelectrification of the milled material. This leads to generation of charge on the surfaces of active pharmaceutical ingredients and excipients. Charged materials tend to adhere firmly to metallic surface of containers and equipment reducing the process efficiency or even resulting in clogging and stoppages.  Therefore, mitigating electrostatic charging is highly desirable for improving the pharmaceutical manufacturing process and ensuring consistent product quality.

 In this study, wet co-milling is investigated as a potential method to reduce the electrostatic chargeability of ibuprofen (IBU). IBU is selected as the model compound as it possesses high cohesivity as well as poor powder flow during the manufacturing process.  Sieved fraction (63-106 µm) of IBU prepared by a Retsch® sieve shaker was milled using a planetary ball mill in the presence of water and/or selected polymers for 15 min at ball-mass ratio of 50:1. After vacuum drying for 2 hours, physicochemical characterization of the milled material was conducted: electrostatic charge (Faraday’s Cage and Electrometer), particle size (Laser Diffraction), moisture content (Karl Fischer Titration), crystallinity (X-Ray Powder Diffraction; XRPD), morphology (Scanning Electron Microscopy; SEM), chemical interaction (Fourier Transformed Infrared Spectroscopy; FT-IR), surface adsorption behavior (Gravimetric Vapor Sorption) and thermal analysis (Differential Scanning Calorimetry; DSC). 

Results showed that as compared to sieved IBU, (dry) milling increased the electrostatic charges by 10.3%, wet milling with de-ionised water alone (water content of 5 wt.%) showed a 60.3% charge reduction. Addition of polyvinylpyrrolidone (PVP) at 0.15 wt.% resulted in a further 96% charge reduction. The reduction in chargeability may be attributable to two effects:  firstly, the increase in moisture content by wet-milling; and secondly, a possible reduction of residual solvent content by wet co-milling with PVP.  The latter is still under investigation.  This study demonstrated the potential of wet co-milling with a suitable polymer to significantly reduce the electrostatic chargeability of milled pharmaceutical materials.