Bench to batch: Linking pharmaceutical powder flow characterisation, intermediate bulk container discharge and video observations.

Five well known excipients and a model drug substance with varied particle properties and bulk behaviour were chosen for the study. Based on the results APAP, NaCMC-XL, mannitol and DCPA were selected for a design to understand the impact of different blends. Two pilot scale unvented IBCs were used in the study. The IBC discharge rates were measured using a catch balance and the mode of flow and powder behaviour inside the IBC was recorded using a camera. The videos inside the IBC showed that regardless of flow mode, for powder to flow from the IBC an air burst was necessary. This was similar to observations when emptying water from a bottle. The extent of the air flow inside the IBC was strong and could possibly result in fluidisation segregation. The discharge curves of 15° and 30° hopper half angles were very similar, which was explained by the vertical air movement in the steeper hopper, which reduces the particle acceleration. Several good indicators of flow/no flow in the IBCs were found. However, for predicting the discharge rate there was a linear correlation between flow through an orifice and IBC discharge rate.

Independent Tailoring of Dose and Drug Release via a Modularized Product Design Concept for Mass Customization.

Independent individualization of multiple product attributes, such as dose and drug release, is a crucial overarching requirement of pharmaceutical products for individualized therapy as is the unified integration of individualized product design with the processes and production that drive patient access to such therapy. Individualization intrinsically demands a marked increase in the number of product variants to suit smaller, more stratified patient populations. One established design strategy to provide enhanced product variety is product modularization. Despite existing customized and/or modular product design concepts, multifunctional individualization in an integrated manner is still strikingly absent in pharma. Consequently, this study aims to demonstrate multifunctional individualization through a modular product design capable of providing an increased variety of release profiles independent of dose and dosage form size. To further exhibit that increased product variety is attainable even with a low degree of product modularity, the modular design was based upon a fixed target dosage form size of approximately 200 mm3 comprising two modules, approximately 100 mm3 each. Each module contained a melt-extruded and molded formulation of 40% w/w metoprolol succinate in a PEG1500 and Kollidon® VA64 erodible hydrophilic matrix surrounded by polylactic acid and/or polyvinyl acetate as additional release rate-controlling polymers. Drug release testing confirmed the generation of predictable, combined drug release kinetics for dosage forms, independent of dose, based on a product's constituent modules and enhanced product variety through a minimum of six dosage form release profiles from only three module variants. Based on these initial results, the potential of the reconfigurable modular product design concept is discussed for unified integration into a pharmaceutical mass customization/mass personalization context.