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. The objective of this paper is to examine the feasibility of using dry coating based surface modification of microcrystalline cellulose, Avicel PH-105, to produce an engineered fine grade (< 30μm) excipient that has all three desired properties. Using a material sparing high-intensity vibrational mixer, Avciel PH-105 is dry coated with 1 wt % Aerosil 200, selected due to its relatively higher dispersive surface energy and lower particle size amongst other silica choices. The results indicated that as expected, the bulk density and flowability are 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 reduced silica amount was examined. Remarkably, at reduced levels (0.5 wt % to 0.7 wt %) of Aerosil 200, significant improvements in bulk density and flowability were attained with only 9%-12% compaction reduction. The properties of the surface-engineered excipients were compared with several other commercially available pharmaceutical excipients using two different processibility or regime maps; tablet tensile strength versus bulk density or flow function coefficient (FFC). The surface engineered excipients exhibited the best overall performance establishing a promising pathway to engineer excipients using dry processing instead of complex processes such as spray drying.

The results presented in this study have shown that dry coating process, which is a solventless, environmentally friendly technique, makes it possible for an exemplary fine excipient having high surface area to achieve good flowability, high bulk density as well as good compaction properties. As an example, a new high functional fine excipient was developed by dry coating Avicel PH-105 with Aerosil 200 in very low amount in the range 0.5 wt % or 0.7 wt % using LabRAM as a single step material sparing technique. It was shown that judicious use of the selected grade of silica, validate through comparative experimental assessment of Aerosil 200, R972 P, and M-5P, allows for achieving maximum enhancements in flow and bulk density while keeping the loss of compaction properties under 10 % as compared to as received fine excipient. Thermo-gravimetric analysis indicated that dry coating with hydrophilic silica leads to a slight increase in the moisture content, which can have negative impact on flowability yet positive impact on tablet strength. However, any such potential effects appear to be outweighed by the change in surface roughness and surface energy after dry coating. The new surface engineered excipients exhibit the best performance in terms of bulk density, flowability as well as compaction property compared to several well-known commercially available excipients, shown through two processibility or regime maps. Overall, the dry coating process shows great benefit for industrial processing since it is environmental friendly and requires fewer steps than popular approach such as spray drying that requires use of liquids, drying, and sieving. Finally, the amount of silica used here is 0.7 wt % or less, which enhances the design space for the final formulation since the total amount of silica has to be kept within 2 wt %.

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