Evaluation of different types of mannitol for dry granulation by roller compaction

Abstract

Dry granulation by roller compaction (RC) is a continuous manufacturing technology increasingly used in the pharmaceutical industry for improving bulk density and flowability of powder mixtures or for preventing segregation issues of highly potent drugs prior to tableting. Dry granulation is ideally applied to moisture and heat sensitive drugs with added benefits also in terms of costs and lower equipment footprint. Mannitol is a polyol widely used in pharmaceutical formulations: particularly in orally dispersible tablets and powders and chewable tablets, where its high solubility and pleasant organoleptic properties make it an excipient of choice. Mannitol is available in several grades with different technological characteristics for adapting to various applications. In view of the use of mannitol for the formulation of active ingredients with poor flowability and compaction, the present work was aimed at analyzing the properties of the different commercial types of mannitol when used for dry granulation by roller compaction to obtain tablets. Mannitol raw materials and granules prepared by roller compaction at different pressure were characterized for particle size distribution, bulk density, flow properties, specific surface area and ability to tableting. Granules with proper size (500–1500 μm), increased bulk density and adequate flow properties could be obtained. Increased specific surface area of the granules suggested a fragmentation of the particles during roller compaction even at relatively low processing pressure confirming the brittleness of the materials. For all materials tested, satisfactory properties for enabling tableting process were shown.