Dry Milling of Analgesics for Particle Size Reduction on the Bead Ruptor 96

Milling processes are widely employed in pharmaceutical production and testing to reduce particle size to increase solubility or stabilization and for component analysis [1-2]. As most drugs compounds must be comminuted at some point in the production or QC process, optimization of milling parameters and the correlation of these parameters with effective particle size distributions is critical. While the milling process is operable under dry and wet conditions, physio-chemical properties of the particle during dry milling are affected by parameters both easily attainable and manipulated (type of milling equipment, milling energy, processing time, ball-powder ratio, and particle rigidity) [3]. While milling wet suspensions will achieve smaller particle diameters across multiple concentrations when compared with the corresponding dry-milled samples [4], dry milling is preferred as it maintains product integrity and easier to scale in a production environment.

In this investigation, the efficacy of the dry milling protocol in the reduction of analgesics was examined, in part, as a feasibility study to determine an adequate range of sample composition over which the Omni Bead Ruptor 96 can operate. Herein, we evaluate the time course over which the milling frequency of samples of consistent mass produced a reduction in particle size. The average particle diameter was measured via 1:1 (mg:mL) dilution in a cuvette prepared for a Particle Size Analyzer (Shimadzu SALD-7500nano).

Table 1: Sample Processing at 30 seconds.