Evaluation of Granulated Lactose as a Carrier for DPI Formulations 1: Effect of Granule Size

Abstract

ABSTRACT. The objective of this study was to investigate the effect of large granulated lactose carrier particle systems on aerosol performance of dry powder inhaler formulations. Granulated lactose carriers with average sizes ranging from 200 to 1,000 μm were prepared and subsequently fractionated into separate narrow size powders. The fractionated granulated lactose (GL) samples were characterized in terms of size, specific surface area, surface roughness, morphology, density, flowability, and solid-state. The in vitro aerosolization performance was performed on the different size fractions of GL samples from a commercial inhaler device (Aerolizer®) with a model formulation (2% w/w salbutamol sulfate). The cascade impaction parameters employed were 60 or 90 L/min with standard (aperture size, 0.6 mm) or modified piercing holes (aperture size, 1.2 mm) of the inhaler loaded capsules. It was shown that the largest size fraction formulation (850-1000 μm) had a slight improvement in the fine particle fraction (FPF) compared to immediately preceding size fractions, explained by a smaller adhesive force between drug and carrier. Compared to commercial piercing holes, enlarged piercing holes generated a slight decreasing trend of FPF as the lactose powder sizes increased from 200-250 μm to 600-850 μm, perhaps due to the reduced detachment force by flow forces. The size, surface roughness, density, and flowability of lactose carrier as well as device design all contributed to the aerosol dispersion performance of granulated lactose-based adhesive mixtures. It was concluded that poorer or enhanced redispersion performance is not an inherent property to the significantly large size of granulated lactose carriers as previously contended.

On the effects of blending, physicochemical properties, and their interactions on the performance of carrier-based dry powders for inhalation — A review

“…Decreasing the size of carrier particles was shown to lead to increased [18,41,61,81,130,[140][141][142][143][144][145][146][147], decreased [135,143,144], and similar [64,80,[148][149][150][151][152][153] FPFs of drug. This is because the degree by which carrier size affects the dispersion of a DPI formulation is influenced by other interacting variables such as the type of drug [154], type of inhaler [144], the chemical nature of carrier [155], and the amounts of fine excipient additives [156].…”

Evaluation of Granulated Lactose as a Carrier for Dry Powder Inhaler Formulations 2: Effect of Drugs and Drug Loading

“…23 Recently, carriers with a large size fraction (>200 mm), especially with significantly rough surfaces, have shown improved aerosol performance. 5,24 This improvement is explained by the switch of the predominant detachment mechanism from turbulence flow to impaction force. 5 Meanwhile, on account of the extremely small cohesive force/weight ratio, these large carrier particles exhibited better flow properties than their smaller counterparts.…”

“…A previous study found that significantly larger granulated lactose with super macro roughness improves uniformity and aerosol performance when using a low dose of model drug. 24 Super macro roughness was defined by the distance between 2 rough peaks being 1000 times larger than the size of drug particle. Contrary to macro roughness, the super rough surface of the large granulated lactose carriers actually improved aerosol performance by sheltering more drug particles from press-on forces better than their smooth counterparts.…”

“…Contrary to macro roughness, the super rough surface of the large granulated lactose carriers actually improved aerosol performance by sheltering more drug particles from press-on forces better than their smooth counterparts. 11,24 A pollen-shaped carrier prepared with hydroxyapatite particles has been proposed as a high drug loading carrier with superior aerosol performance to the lactose carriers with a rocklike shape. 33,34 Previous studies have also reported that porous carrier particles exhibited an improved drug loading compared to smooth particles, during an interactive mixing, without compromising blending uniformity.…”

“…Additionally, the surface roughness/granule cavity volumes of granulated lactose is positively correlated to granular size. 24 Thus, improved blending uniformity and high drug loading could be achieved using significantly larger granulated lactose (e.g., 200-1000 mm) for DPI formulations.…”