Accuracy assessments for laser diffraction measurements of pharmaceutical lactose

Abstract

The accuracy of laser diffraction size measurements of dry powder inhaler particles, which play an important role in guiding effective inhaler system design, is assessed. Additionally, data for lactose particle shape characteristics are presented. Comparisons made between microscopy and cohesion-minimized laser diffraction size measurements for pharmaceutical lactose particles indicate that non-sphericity causes a broadening of the size distribution while the median diameter is unchanged. This is corroborated by data in the literature. Poured particles and those dispensed from an inhaler shared a common characteristic agglomerate modal diameter that was absent in the cohesion-minimized wet suspension. It is concluded that the interpretation of integral measurements of the particle size distribution using laser diffraction, for cohesive particle systems, is reasonable. The method of dispensing particles from an inhaler and delivery through an artificial throat is critical and both decreased the proportion of agglomerates present.

WITHDRAWN: 3D characterisation of dry powder inhaler formulations: Developing X-ray micro computed tomography approaches

“…The lower modal and percentile values for XCT are due to it measuring the actual volume of the particle. On the other hand, the assumption of particle sphericity used in both LD and OM means that the reported sizes are overestimates of the actual particle sizes [62]. This is the main reason that the XCT distributions lie to the left of LD and OM, rather than being due to the resolution limits of either technique.…”

“…The most commonly used techniques for characterising physical powder attributes are laser diffraction (LD), scanning electron microscopy (SEM), optical microscopy (OM) and cascade impaction (CI), but each have their own limitations; for example LD measurements provide the volume-based particle size distribution, but suffer from shape-bias [62] as the technique assumes spherical particles as opposed to the tomahawk shape typical of lactose crystals [51]. Microscopy-based techniques like SEM and OM are based on the 2D image analysis of particles dispersed on a substrate to produce particle size distributions and shape metrics such as aspect ratio and circularity.…”

Effect of Device Design and Formulation on the In Vitro Comparability for Multi-Unit Dose Dry Powder Inhalers

“…These 30-μm particles were chosen for particle tracking simulations since they represent the fines mass fraction generated within inhaler airflow paths as suggested by Stevens et al (22). Monodispersed particles were used to allow simple comparison between the different device designs.…”

Non-impactor-Based Methods for Sizing of Aerosols Emitted from Orally Inhaled and Nasal Drug Products (OINDPs)

“…Although the manufacturers of LD equipment point out the advantage of not requiring calibration because the technique is absolute in nature, the accuracy of such measurements of dry powder inhaler lactose carrier particles in the range 20 to 250 μm diameter has recently been investigated systematically (54). Comparisons were made between sizes derived from microscopy-automated image analysis, taking precautions to control particle cohesion.…”