(298e) Improving Blend and Tablet Properties of Binary Mixtures Containing Cohesive and Poorly-Compactable APIs Using Surface Engineered MMC Based Fine Excipients

Improving blend and tablet properties of binary mixtures containing cohesive and poorly-compactable APIs using surface engineered MMC based fine excipients

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

Abstract

High functional excipients with good flow, high packing density, and excellent compaction have been developed via dry particle coating in recent work [1]. Even though these new fine grades of excipients demonstrate high functional properties in placebo tablets compared to other silicified excipients such Prosolv 50, and Prosolv 90, it is questionable that these high functional properties will preserve in blends with cohesive and poorly-compactable active pharmaceutical ingredients (APIs). The objective of this presentation is to study the effect of MCC-based, fine engineered excipients on improving the properties of blends and tablets in binary mixture with cohesive and poorly compactable APIs. Ibuprofen 50, and two grades of Acetaminophen were selected as model APIs and Avicel PH-105 dry coated with 1wt% hydrophilic silica A200 was used as the engineered excipient in preparing binary mixtures at three different drug loadings (10%, 30%, 60%). The functional properties of the blends were compared with the blends made with as received Avicel PH-105, Prosolv 50 and Prosolv 90, respectively. The results indicated that as expected, the bulk density and flow of binary mixtures of engineered excipient, dry coated Avicel PH 105, were significantly improved as compared with as received Avicel PH-105 while there was a slightly decreased tablet strength at lower drug loadings. Most interestingly, at higher drug loading, there was an improvement in tablet strength. When compared with commercial high functional excipients, Prosolv 50 and Prosolv 90, at low drug loadings, the surface engineered excipients still exhibited a better or comparable bulk density, flow properties, and tablet strength. However, as drug loading increased commercial silicified excipients showed adverse effect on blends and tablet properties. In contrast, the surface engineered excipients demonstrated significant improvement in all three desired properties, suggesting improved manufacturability. Overall, it is hoped that these new very fine surface modified engineered excipients will promote high-speed direct compaction tableting of cohesive APIs at relatively high drug loadings.

1. Chen, L., et al., Surface engineered excipients: I. improved functional properties of fine grade microcrystalline cellulose. International Journal of Pharmaceutics, 2018. 536(1): p. 127-137.