Can a Lipid-Containing Co-Processed Excipient Overcome Compression Challenges Associated with a Cohesive and Viscoelastic API?

Although direct compression is the preferred method for manufacturing tablets, it has very limited application due to the poor flowability and compaction properties of most active pharmaceutical ingredients (APIs). Co-processed excipients have emerged as a possible way to overcome these challenges. In the present study, acetaminophen was selected as a model API to evaluate the potential of a novel lipid-containing co-processed excipient to compensate for unfavorable API properties, such as high cohesiveness and viscoelastic properties. Flowability tests and a comprehensive evaluation of tableting properties, including the USP-recommended compression characterization approach and dynamic compaction analysis, were performed. In addition, the potential of this novel co-processed excipient was compared to the commercially available co-processed excipient RetaLac®. The results showed that the novel co-processed excipient has superior flowability in the presence of acetaminophen compared to RetaLac®. The tensile strength of tablets with the lipid-containing co-processed excipient was significantly influenced by acetaminophen content, and an acceptable value (> 1 MPa) was achieved with 30% API, while a slightly higher tensile strength was obtained with RetaLac®. However, a multifold higher network of compression, detachment and ejection stresses in the case of the commercial vs. novel co-processed excipient indicate a much higher ability of the latter to overcome problems associated with the high adhesiveness of the API. Elastic recovery was significantly affected by compression speed, but strain rate sensitivity analysis indicated that not only the compression speed but also dwell time may be important in achieving acceptable mechanical properties of tablets containing viscoelastic API.