Mannitol in direct compression: Production, functionality, critical material attributes and co-processed excipients

Abstract

In recent years, mannitol has been widely used in the pharmaceutical industry as a substitute for lactose. Mannitol is widely available and can be produced by a variety of methods. Due to its water solubility, low hygroscopicity and chemical inertness, it is commonly added to various formulations, especially tablet formulations. A better understanding of the Critical Material Attributes (CMAs) of raw materials can help guide tablet quality improvement and mannitol development based on quality by design. In addition, co-processing of mannitol can introduce more desirable properties to the resulting particles. In this review, we focused specifically on the recent advances and development of mannitol on direct compression (DC) tableting, including the functions in tablet formulations, potential CMAs, and mannitol-based co-processed excipients, therefore providing a reference for further studies.