Effect of compression pressure on inhalation grade lactose as carrier for dry powder inhalations

Abstract

Introduction:This study focused on the potential effects of compression forces experienced during lactose (InhaLac 70, 120, and 230) storage and transport on the flowability and aerosol performance in dry powder inhaler formulation.Materials and Methods:Lactose was subjected to typical compression forces 4, 10, and 20 N/cm2. Powder flowability and particle size distribution analysis of un-compressed and compressed lactose was evaluated by Carr's index, Hausner's ratio, the angle of repose and by laser diffraction method. Aerosol performance of un-compressed and compressed lactose was assessed in dispersion studies using glass twin-stage-liquid-impenger at flow rate 40-80 L/min.Results:At compression forces, the flowability of compressed lactose was observed same or slightly improved. Furthermore, compression of lactose caused a decrease in in vitro aerosol dispersion performance.Conclusion:The present study illustrates that, as carrier size increases, a concurrent decrease in drug aerosolization performance was observed. Thus, the compression of the lactose fines onto the surfaces of the larger lactose particles due to compression pressures was hypothesized to be the cause of these observed performance variations. The simulations of storage and transport in an industrial scale can induce significant variations in formulation performance, and it could be a source of batch-to-batch variations.

Modulated Uniaxial Compression Analysis of Respirable Pharmaceutical Powders

“…In such a case, it is important to use low compression pressures when packaging the powder product to achieve particle rearrangement, resulting in a loose powder compact. Utilizing low pressures when plastically compressing respirable powders can also mitigate the deformation or fracturing of the particles (Chen et al, 2017;Raut et al, 2016;Sørensen et al, 2005;Vu et al, 2020), preserving the aerodynamic properties of the particles, while minimizing the volume of powder needed for each capsule. As a result, single-value density measurements, such as bulk and tapped density, are unsuitable for relatively cohesive respirable powders, so new methods are required for accurate and reproducible Compressed Bulk Density (CBD) measurements.…”