Capsule Filling of Spray Dried Powders for Inhalation using a Drum Filling technology:
From Lab to Pilot Scale
Rui Churro1, Carolina Lopes1, Maria Inês Lopes1,2, Susana Saldanha1 & João Pires1
1 Hovione FarmaCiência S.A., Estrada do Paço do Lumiar, Campus do Lumiar, Edifício R, 1649-038 Lisboa, Portugal
2 Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais 1, 1049-001, Lisboa, Portugal.
Spray dried composite formulations are an attractive alternative for dry powder inhalers (DPIs) since these can be obtained in a semi-continuous operation where it is possible to manipulate process parameters to tailor-made particles with the desired properties for aerosolization. However, these powders typically have low density and poor flowability, creating operational challenges in downstream processes such as capsule filling. It is then important to characterize which are the main challenges in processing these materials both at lab and industrial scale. The current study aims at deeply understand process development across lab and pilot scale, of a capsule filling process of spray dried composite powders for pulmonary drug delivery, by means of drum technology. For that, capsule filling process performance was evaluated in terms of relative standard deviation (RSD) and aerodynamic performance, using both a lab- and a pilot-scale process equipment train under different conditions. Formulation comprised trehalose dihydrate/L-leucine (80:20 %w/w). The obtained results contribute for the choice of the most appropriate process parameters regarding drum-based capsule filling for powders intended for inhalation and for the implementation of a suitable strategy for the upscaling of low dose DPI product using this technology.
Representative powders for inhalation were successfully filled with drum filling technology in both pilot-scale and lab-scale equipment. Critical process parameters such as vacuum pressure and powder sieving across scale were identified and lab-scale as a worst case in terms of process performance.