Micronization of a soft material: air-jet and micro-ball milling

Abstract

The air-jet and ball-mill are frequently used in fine micronization of active pharmaceutical ingredients to the order of 1-5 microm, which is important for increasing dissolution rates, and also for pulmonary delivery. In this study, we investigated the ability of air-jet and ball-mill to achieve adequate micronization on the lab scale using a model soft material, Pluronic F-68. Material mechanical properties were characterized using the nanometer 600. Pluronic F-68 was ball-milled in a micro-mill at different material weights and durations in liquid nitrogen vapor. In comparison, a lab scale air-jet mill was used at various milling parameters according to a full factorial design, where the response factors were particle yield and particle size distribution, which was analyzed using laser diffraction and scanning electron microscopy. The yield achieved with the micro-ball mill was 100% but was ~80% for the air-jet mill, which reduced the size of Pluronic F-68 from 70 microm to sizes ranging between 23-39 microm median diameters. Ball milling produced particles less than 10 microm after 15 min. Although air-jet milling proved capable of particle size reduction of the relatively soft material Pluronic F-68, limitations to the lower size range achievable were observed. The feed rate of the material into the air jet mill was a significant factor and slower feed rates lead to smaller sizes by allowing more time for particle collisions and subsequent particle breakage to occur. Micro-ball milling under cold condition was more successful at achieving a lower range particle size reduction of soft materials.

Fig. 1

Load–displacement profile of Pluronic® F-68 using the Nanotester 600

Fig. 2

Dv50 (a cube, b contour plot) and Dv90 (c cube, d contour plot) values of micronized Pluronic® F-68 at different feed rate, grinding ‘1’, grinding ‘2’, and at high pusher pressure (100 psi)

Fig. 3

SEM micrographs of bulk Pluronic® F-68 (a) and air jet milled (b) The scale bar is 50 μm

Fig. 4

SEM micrographs of cryo-micro-ball milled Pluronic® F-68 after 15 min for 25 mg (a), 50 mg (b), and 100 mg (c)