Milling: Particle engineering beyond size reduction

Abstract

Milling or physically dividing solids into fine fragments is the best-known methodfor the production of powders. It is found widely across industries from pharmaceuticals,nutraceuticals, agrochemicals, aerosols, personal care products, pigments, ceramics,cement to semi-conductors. Traditionally, milling (or also known as grinding) is regardedas a particle size reduction process, which increases the specific surface area of a solidphase for desired interaction with the neighboring phase. Advanced powdercharacterization techniques have revealed that milling performs more than just a sizereduction role. The mechanical and thermal energies imposed onto a milled powder alterother physicochemical properties like morphology, crystallinity, polymorphism, glasstransition temperature, surface energy, melting properties, as well as lead to particle sizeshift and changes in specific surface area during subsequent storage. These changes oftenhave a pronounced effect on the product performance such as powder flow,aerosolization, dissolution, physical and chemical stability. The underlying scientificknowledge behind these changes has created avenues to engineer new applications aswell as mitigate the milling-induced effects that are detrimental to product performance.This review presents recent developments in milling technologies such as nanomilling,co-milling and post-milling conditioning. Nanomilling using stirred media mills withsuitable surfactants has produced stabilized nanosuspensions below the postulatedgrinding limit of half a micron, and thereby increases the specific surface area by up to10-fold and the saturated solubility by 6-fold. Co-milling or simultaneous milling of twoor more solid component has been effective in controlling the solid-state properties ofmilled powders. Milling-induced amorphization or the loss of long-range crystallinestructure is often associated with stability problems as the amorphous phase isthermodynamically unstable and tends to re-crystallize to the stable crystalline form. Thiseffect can be mitigated by co-milling with crystalline seeds. On the other hand, when anamorphous product is desired as it has advantages of higher solubility, dissolution rateand better compression characteristics over the crystalline form, the addition of polymericadditives during milling has led to stable amorphous solid dispersions. Co-milling withmesoporous materials also results in an amorphous form, which is entrapped insidenanosized channels. Co-grinding has been used to prepare co-crystals, which possessdifferent physicochemical properties from the original components. To alleviateundesired milling-induced effects, new findings in post-milling conditioning as well asrecent research to alternative processes to particle size reduction will be discussed. © 2011 Nova Science Publishers, Inc. All rights reserved.