(443a) Dry Mechanical Processing for Value-Enhanced Excipients

Liang Chen, Xiaoyi Ding, Siqi Fan, Rajesh N. Davé^*

Abstract

Excipients with good flowability, bulk density as well as compaction properties are desired for use in tableting since they play important roles in formulation development and processing, including, handling, mixing, feeding and compaction. However, it is often difficult to manufacture excipients that simultaneously possess all three desirable properties. In addition, most commercially available excipients that have excellent flow as well as compaction properties require multi-step processing involving use of solvents and subsequent drying, milling and sieving. The objective of this work is to examine the feasibility of using dry coating based surface modification of microcrystalline cellulose (MCC) using commercially available grades such as Avicel PH-101, PH-102 and PH-105, to produce engineered excipients having desired properties. Such an approach allows for preparing novel excipients without use of solvent and are expected to have lesser environmental footprint. Using a material sparing, model based dry coating methodology, as-received grades of MCC were dry coated with 1wt% silica R972P and Aerosil 200, along with selected cases using M-5P. The results indicated that as expected, the bulk density and flowability of dry coated MCCs were significantly improved, while there was an appreciable loss of compaction. To minimize the loss of compaction, attributed to decreased surface energy after coating, while maintaining improved bulk density and flowability, the effect of the type of silica was examined. Remarkably, use of Aerosil 200 led to significant improvements in bulk density and flowability with minimal reduction in compaction. The properties of the surface-engineered excipients were compared with as received and selected commercially available specialized pharmaceutical excipients. It was found that surface engineered excipients have a potential to achieve as good overall performance as any other materials in the market. Selected additional excipient materials are tested and overall, this work demonstrates feasibility for engineering excipients using dry processing instead of complex processes such as spray drying.