Method to Evaluate the Dustiness of Pharmaceutical Powders

Abstract

The trend among pharmaceutical companies to develop selective drugs of high potency has pushed the industry to consider the potential of each hazardous ingredient to become airborne. Dustiness issues are not unique to the pharmaceutical industry, but are relevant to any industry where powdered materials are mixed, transferred and handled. Interest in dustiness is also driven by concerns for worker health, the potential for plant explosions and the prevention of product loss. Unlike other industries, the pharmaceutical industry is limited by the milligram quantity of powdered material available for testing during product development. These needs have led to the development of a bench-top dustiness tester that requires only 10 mg of powder and fully contains the generated aerosol. The powder is dispersed within a 5.7 liter glass chamber that contains a respirable mass sampler and a closed-face sampler to quantify the respirable and total dust that are generated with a given energy input. The tester distinguished differences in dustiness levels of five different powders. Finer powders were dustier, and the respirable dust percentage was always less than that for total dust. Four testers have been built and evaluated using pharmaceutical grade lactose. Dustiness measurements determined using all four testers were comparable. The pharmaceutical industry uses surrogates such as lactose to represent active compounds in tests that estimate the dust concentration likely to occur in a new manufacturing operation. Differences between the dustiness of the active compound and its surrogate challenge the relevance of the surrogate tests to represent true exposures in the workplace. The tester can determine the dustiness of both the active compound and its surrogate, and the resultant ratio can help to interpret dust concentrations from surrogate tests. Further, dustiness information may allow the pharmaceutical researcher to select powder formulations that present low airborne concentrations in the workplace.

Computational fluid dynamics analysis of the Venturi Dustiness Tester

“…A qualitatively different method was introduced [59] in order to test pharmaceutical powders. Evans et al [60] used this method to study a wide variety of nanoscale powders.…”

“…Aerosolization proceeds under turbulent conditions, whereas in the gentle tests, the airflows are larger scale and laminar. The reproducibility [59] of the method has been criticized [63] but has been defended [64]. The method involves more aggressive air flows than those typically encountered in large-scale workplace activities (however, the use of compressed air to clean contaminated worker clothing or work surfaces approximates the aerodynamic conditions of the VDT).…”

“…The masses of the powder collected on the cyclone filter, M dc , and on the dust sampler, M ds , , are used to calculate [59–60] the respirable and total dustiness, respectively, as…”

Comment on Comparison of Powder Dustiness Methods

“…We have read with interest the recent work by the University of Wuppertal group (Bach et al , 2013) on dustiness determination using the University of North Carolina (UNC) Dustiness Testing Device (Boundy et al , 2006). We have referred to the UNC device as the ‘Venturi’ device (Evans et al , 2013), as that describes the underlying dispersal mechanism; we continue with this terminology.…”

“…1) as a function of the measurement value, D tot . The National Institute for Occupational Safety & Health (NIOSH) RSDs (typically, n ≥ 6, with minor exceptions, see Evans et al , 2013) are all small, except for one extremely low dusty material (Kemira TiO 2 ); the RSDs ( n = 9) for the five materials tested in the original UNC study (Boundy et al , 2006) are similarly small. By contrast, the RSDs ( n = 5) for the Wuppertal pharmaceutical measurements (Wupp-Pharm) are systematically higher and become increasingly poor at lower dustiness values.…”