A Novel Method for Stabilizing Particle Size of Milled Powders

Milling or grinding forms an integral part in pharmaceutical secondary manufacturing. However, occurrence of either particle size increases or reduction during storage had been reported [1]. Changes in the particle size can affect, for instance, the powder homogeneity, dissolution rates, and therapeutic effect in dry powder inhalers. The current practice in the pharmaceutical industry is to store milled powders for durations between 2 weeks to 3 months and the duration can vary from material to material. To the best of the authors' knowledge, no techniques are currently available in the market to shorten or avoid the stabilization time.

We propose fluidization after ball milling as a simple mechanical agitation method to stabilize the particle size of adipic acid (1, 6-hexanedioic acid) powders. Recrystallized adipic acid crystals are ball milled with ball to powder mass ratio of 50:1 for 30 min. Next, the milled powder is fluidized with dry compressed air in a bench scale fluidized bed at a flow rate of 30 L/min (+/- 5 L/min) for a period between 1 to 4 hours. The milled and fluidized product is sieved for a particle size range before allowing storage at relative humidities of 25% and 75% and temperature of 22 ^οC for a period of 7 days. Particle size measurements using wet dispersion laser diffraction method revealed that the stored samples subject to fluidization after milling have significantly less amount of fines (< 100 μm) than those without fluidization. In addition, the amount of fines seems to decrease as the fluidization period is increased. Scanning electron microscopy images of the surfaces show that the primary fine particles of the fluidized samples appear to be more packed after storage. It is postulated that during fluidization, particle-particle and particle-wall collisions aid in compacting the loose fines on the bulk primary particle surfaces, leading to more stable agglomerates even after storage. [1]. Ng et al., Pharm. Res., 25, 5, 1175-1185, 2008