Combinational Approach for Advanced Understanding of a Capsule Filling Process for Inhalation Application

Synopsis

Delivery of medicinal products through the lungs, via capsule based Dry Powder Inhaler devices represent one of the most rapidly expanding fields in pulmonary drug delivery. The precise filling of capsules with doses in the milligram-range needed for inhalation application relies on a well understood filling process. Among the several low-dose capsule filling systems currently available, the dosator principle plays an important role. One of the greatest challenges for successfully manufacturing high-quality low-dose inhalation products is dose uniformity. During a dosing step a combination of various stresses between the powder and the equipment material, results in more or less stable plugs which can be lifted by the nozzle to be filled into a capsule. The powder is kept in the dosator nozzle because of the formation of a stable arch at the outlet, which is dependent on powder characteristics and the vertical stresses which are transmitted through the powder bed. In order to understand the interplay between filling process and filling material a combinational approach, which comprises an in-depth analysis of the process based on experimental and in silico simulation studies was used: 1) To experimentally investigate the effect of different material properties and process parameters on the quality of the final product using a lab-scale, capsule filler; 2) In silico simulations via the Discrete Element Method to support experimentally obtained data and to be able to “look inside” the dosator nozzle. Modelling and simulation studies of the dosator capsule-filling process are rare and a deeper mechanistic understanding of the process is required. With this combined approach, process understanding and mechanistic modelling & simulation a systematic understanding, thus a further step towards a scientific qualification of dosator nozzles capsule filling can be achieved and will help improving the filling performance of challenging powders for DPI applications.