(68a) Enabling Direct Compaction at High Drug Loading Via Dry Coating of APIs: Towards a Predictive Framework

Authors: 
Davé, R. - Presenter, New Jersey Institute of Technology
Kunnath, K., New Jersey Institute of Technology
High speed direct compression (DC) tabletting is widely considered as the most ideal process to produce tablets in the pharmaceutical industry. DC continuous processing route is a natural and economical link between continuous API and drug manufacturing. It is beneficial because it consumes lower energy, resources, time and money compared to alternative processes that may include extra laborious unit operations for granulation and drying. However, due to the cohesive nature of active pharmaceutical ingredients (APIs), achieving drug loading of 30 % or higher via DC route is not possible in batch or continuous processing. These problems get more severe when APIs are micronized for enhanced content uniformity (CU) or bioavailability improvement, and the use of specialized higher performance excipients do not necessarily help. Dry coating of cohesive APIs via solventless continuous process has been proven to significantly improve the flowability of cohesive micronized APIs, as well as the resultant blends. Dry coating with silica is also shown to minimise adverse impact of the native surface properties, e.g., surface energy and roughness, of APIs, leading to a more robust toolbox for property enhancement. Most recent NJIT work targets dry coating for enabling DC at higher drug loading. Our results show that dry coating significantly improves the pharmaceutical blend properties and allows higher API loading into blends. Furthermore, the feasibility of using finer excipients, which helps in reducing segregation tendency and enables better compaction, to formulate high drug loaded blends with excellent bulk properties has been demonstrated. Blends formulated with dry coated micronized APIs and finer excipients consistently had better flowability compared to the same APIs blended with coarse excipients, which contradicts current industrial practices. On the other hand, for very low drug loading, drug content uniformity greatly improved with dry coated micronized APIs. In order to make wider use of DC route as a link between continuous API and drug manufacturing, it is necessary to develop a modelling framework is necessary to predict API and blend properties such as packing and flowability. NJIT team is developing such framework that can allow the determination of the highest API loading for a given set of properties of the API manufactured via continuous manufacturing with and without API dry coating. Alternately, given the target API loading, such models can determine the API size that must be produced during CM, if they need to be dry coated, and if special purpose excipients would be required.