Compression physics in the formulation development of tablets.

Abstract

The advantages of high-precision dosing, manufacturing efficiency, and patient compliance make tablets the most popular dosage forms. Compaction, an essential manufacturing step in the manufacture of tablets, includes compression (i.e., volume reduction and particle rearrangement), and consolidation (i.e., interparticulate bond formation). The success of the compaction process depends not only on the physico-technical properties of drugs and excipients, especially their deformation behavior, but also on the choice of instrument settings with respect to rate and magnitude of force transfer. This review discusses various properties of drugs and excipients, such as moisture content, particle size and distribution, polymorphism, amorphism, crystal habit, hydration state, and lubricant and binder level of the blend that have an influence on compaction. Tableting speed and pre/main compression force profile, also have a bearing on the quality of the final tablet. Mechanistic aspects of tableting can be studied using, instrumented punches/dies, instrumented tableting machines, and compaction simulators. These have potential application in pharmaceutical research and development, such as studying basic compaction mechanism, process variables, scale-up parameters, trouble shooting problem batches, creating compaction data bank, and fingerprinting of new active pharmaceutical ingredients (APIs) or excipients. Also, the mathematical equations used to describe compaction events have been covered. These equations describe density-pressure relationships that predict the pressures required for achieving an optimum density. This understanding has found active application in solving the analytical problems related to tableting such as capping, lamination, picking, sticking, etc. Mathematical models, force-time, force-distance, and die-wall force parameters of tableting are used to describe work of compaction, elasticity' plasticity, and time dependent deformation behavior of pharmaceuticals. Various indices of tableting performance such as the bonding index, brittle fracture index, and strain index can be used to predict compaction related problems. Compaction related physico-technical properties of commonly used tableting excipients have been reviewed with emphasis on selecting suitable combination to minimize tableting problems. Specialized tools such as co-processing of API and excipients can be used to improve their functionality.