Ordered mixing: mechanism, process and applications in pharmaceutical formulations

Abstract

Ordered mixing is an alternative to perfect mixing to achieve a more homogeneous mixture than that obtained by random mixing. An ordered mix can be achieved by dry mixing, triboelectrification, milling, adhesion, coating, and fluidization processes. Ordered mixing regulates the particle size of the drug and alters the particle shape to minimize segregation and agglomeration. Factors like shape, size, surface texture, crystallinity, particle attraction and proportion of components affect the quality of ordered mixtures. Processing parameters like blending time, shear forces and mechanism of mixing also play a significant role in forming ordered mixtures. Ordered mixtures are used to increase the dissolution rate of poorly soluble drugs by using a water-soluble carrier and the appropriate covering of the coarser carrier particles with drug. In micro-dose formulations, ordered mixing increases the homogeneity of the powder blend and, thus, it is used to control the content uniformity within pharmacopoeial limits in the finished dosage forms. Surface texture improvement is also beneficial in pharmaceutical and cosmetic applications. Ordered mixtures have also found their use in bioadhesive, sublingual and other fast dissolving formulations in order to improve drug absorption. This review provides an overview of ordered mixing vis a vis current advances in the field of drug delivery and formulation.