Particle Engineering for Enabling a Formulation Platform Suitable for Manufacturing Low-Dose Tablets by Direct Compression.

Maintaining good content uniformity (CU) is a significant challenge for low-dose oral tablets in particular when using direct compression (DC). Using 6 model active pharmaceutical ingredients, we show that a platform DC tablet formulation suitable for developing low-dose API with excellent CU can be developed. This platform formulation is enabled by particle engineering, where an API of interest is loaded in a suitable porous carrier to form a uniform API-carrier composite. Powder properties of such composite particles are dictated by the properties of the carrier, which are insensitive to chemical structure and loading level of the API. Powder flowability, tabletability, tablet friability, and tablet disintegration time are all excellent and only vary within a narrow range among the 6 model APIs. Nearly 100% drug can be released in water from tablets composed of the 6 model APIs. Thus, the approach described here holds the promise for broad application in developing low-dose tablet products using DC possessing excellent CU and other critical quality attributes.