(156i) Preparation and Use of Fine Grade Engineered Excipients for Direct Compression of Binary Blends of Cohesive Drug Powders

Novel, surface modified excipients are prepared using a fluid energy mill (FEM) to simultaneously mill and dry coat microcrystalline cellulose (MCC) with nano-silica to produce different sizes of fine, well flowing MCC excipient [1]. The purpose of these new class of excipients is to enable direct compression (DC). DC route is one of the most efficient and economic methods for tablet manufacturing since only blending and compression operations are required, greatly simplifies the process-train. However, the popularity of direct compression is limited by its stringent requirements, such as good flowability, high packing density, and excellent compaction for excipient-active pharmaceutical ingredient (API) blends. When the blend has high drug loading with a poorly flowing API, the flowability and tabletability of blends is generally decreased sharply. In a recent work, it has been shown that surprisingly, fine excipients of 20 mm size that have improved flow and bulk density after silica dry coating, can greatly improve direct compression performance [2]. Unfortunately, it could not work for very fine cohesive APIs such as 10 mm acetaminophen (APAP) at higher drug loading. In this work, binary blends of several fine sized dry coated MCC-based excipients are considered with three different fine, cohesive APIs at high drug loadings. Bulk density, FFC, and tablet compactability for all these blends are measured and compared to determine which excipient sizes provide the best overall performance. The results are analyzed for the relative sizes of the excipients and APIs to better understand the interplay between the components of the blends and assessment of the extent of silica transfer from coated excipient powders to API powders and its effect on blend bulk density and flowability. It is expected that using such novel surface engineered fine excipients in blends with fine APIs may also help in reduced segregation tendency during overall processing. Hence, these results are expected to provide industry relevant guidelines for the use of finer surface modified excipients in DC tableting.