Triboelectrics: The influence of particle surface roughness and shape on charge acquisition during aerosolization and the DPI performance

Pharmaceutical powders are typically insulators consisting of relatively small particles and thus they usually exhibit significant electrostatic charging behaviours. In the inhalation field, the measurement of electrostatic charge is an imperative stage during pharmaceutical formulation development. The electrostatic charge is affected by the interplay of many factors. This article reviews the factors affecting the electrostatic charging of pharmaceutical powders with a focus on dry powder inhalations. The influences of particle resistivity, size distribution, shape distribution, surface roughness, polymorphic form and hygroscopicity, as well as the effects of moisture uptake, environmental conditions, pharmaceutical processing (i.e., milling, sieving, spray drying and blending), and storage on the electrostatic charge behaviours of pharmaceuticals, with focus on inhalation powders, were reviewed. The influence of electrostatic charge on the performance of dry powder inhaler formulations in terms of drug content homogeneity, the passage of drug through the inhaler device, drug-carrier adhesion/detachment, and drug deposition on the respiratory airways were discussed. The understanding gained is crucial to improving the safety, quality, and efficiency of the pharmaceutical inhalation products.

Section: Particle Shape Distributionsupporting

confidence: 62%

A review of factors affecting electrostatic charging of pharmaceuticals and adhesive mixtures for inhalation

Kaialy

2016

“…The work function of a powder depends on its physical and chemical properties including environmental conditions (Yurteri et al, 2002;Matsusaka and Masuda. 2003;Watano, 2006;He et al, 2014;Karner et al, 2014;.…”

Section: Introductionmentioning

confidence: 99%

“…It has been used in different ways to measure the resultant charge for bulk powders in a number of studies, i.e. Brown, (1997), Rowley (2001), Chow et al (2008), Sarkar et al (2012), Šupuk et al (2012), Zarrebini et al (2013), Karner et al (2014). However, these setups can only be used for net charge measurement and cannot quantify charge distribution in multicomponent systems.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of a new dispersion technique for assessing triboelectric charging of powders

Zafar

Alfano

Ghadiri

2018

In a number of applications, especially in pharmaceutical drug development, there is often a very small powder quantity available for evaluating the manufacturability of new drugs. However, it is highly desirable to be able to quickly evaluate processing issues, and where possible using the smallest powder quantity. In the present work, a proprietary commercial powder dispersion device (the disperser of Malvern© Morphologi G3) is adapted to evaluate the triboelectric charging tendency. A very small powder quantity (as small as 0.1 mg) is dispersed by a pressure pulse of compressed gas such as air or nitrogen. This causes the particles to become air borne and collide with the containing walls, resulting in dispersion and leading to triboelectric charge transfer between the particles and the walls. In this work, the charging propensity of a number of materials is evaluated and the effect of particle surface functional groups on the tribo-electric charge transfer is analysed. Model materials with a well-defined shape (glass ballotini) but with different silane groups deposited on their surfaces as well as a number of organic crystalline particles (such as aspirin, α-lactose monohydrate and paracetamol) are tested. Following dispersion the particles move immediately to a Faraday cup placed directly underneath the disperser. Therefore, particle charge is measured with no decay. The method can differentiate charging of different polymorphs of the same material, different silane groups on the surfaces of glass ballotini and different crystal morphologies obtained from crystallisation from various solvents.

“…It causes the drug particles to aggregate and leads to limited fluidisation and dispersion of the particles (Pilcer and Amighi, 2010;Ali and Gary, 2015;Berkenfeld, Lamprecht and McConville, 2015;Peng et al, 2016). Therefore, carriers (e.g., particle size 50-100 µm or larger up to 200 µm) regarded as key components in the development of DPI formulations are employed as a means of delivering the drug to the lungs and to improve the drug delivery efficiency (Kramek-Romanowska et al, 2011;Karner, Littringer and Urbanetz, 2014;Ali and Gary, 2015;Peng et al, 2016;Mönckedieck et al, 2017). Due to the safety concern about carriers to the lungs and insufficient toxicology data, the amount of carriers used should be minimised in DPI formulations to reduce adverse effects of carriers (e.g., cough) (Balducci et al, 2014;Santos and Edelman, 2014;Al-Tabakha, 2015;Peng et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

1H NMR quantification of spray dried and spray freeze-dried saccharide carriers in dry powder inhaler formulations

Babenko

Peron

Kaialy

et al. 2019

Quantitative analysis using proton NMR (1 H qNMR) has been employed in various areas such as pharmaceutical analysis (e.g., dissolution study), vaccines, natural products analysis, metabolites, and macrolide antibiotics in agriculture industry. However, it is not routinely used in the quantification of saccharides in dry powder inhaler (DPI) formulations. The aim of this study was to develop a 1 H NMR method for the quantification of saccharides employed in DPI formulations. Dry powders as DPI carriers were prepared by spray drying (SD) and spray freeze drying (SFD) using three saccharides: namely D-mannitol, D-sorbitol and D-(+)-sucrose. The calibration curves constructed for all three saccharides demonstrated linearity with R 2 value of 1. The 1 H qNMR method produced accurate (relative error %: 0.184-3.697) and precise data with high repeatability (RSD %: 0.517-3.126) within the calibration curve concentration range. The 1 H qNMR method also demonstrated significant sensitivity with low values of limit of detection (0.058 mM for D-mannitol, 0.045 mM for D-(+)-sucrose, and 0.056 mM for D-sorbitol) and limit of quantitation (0.175 mM for D-mannitol, 0.135 mM for D-(+)-sucrose, and 0.168 mM for D-sorbitol). Pulmonary deposition via impaction experiments of the three saccharides was quantified using the developed method. It was found that SFD D-mannitol (68.99%) and SFD D-(+)-sucrose (66.62%) exhibited better delivered dose (total saccharide deposition in throat and all impactor stages) than SD D-mannitol (49.03%) and SD D-(+)sucrose (57.70%) (p< 0.05). The developed 1 H qNMR methodology can be routinely used as an analytical method to assess pulmonary deposition in impaction experiments of saccharides employed as carriers in DPI formulations.