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

Abstract

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.

Influence of mannitol concentration on the physicochemical, mechanical and pharmaceutical properties of lyophilised mannitol

“…A clear trend of decreased netcharge with increasing the median diameter of LM was established (Figure 2b). This could be attributed to the increase in the overall surface area available for charge-transfer in the case of smaller LM particles due to higher particle-wall contacts, greater particle number density, and higher surface area (Kaialy, 2016). High levels of electrostatic charging of pharmaceuticals intended for direct compression is considered as a nuisance because it leads to their adherence to the punches, dies and feeding hopper, affecting tablet weight and hence drug content uniformity.…”

“…For example, milling offers low opportunity to produce particles with controlled characteristics such as size, shape and surface properties (Snow et al, 1984). Jet-milled particles usually exhibit broad size distributions, irregular shapes (Rasenack and Müller, 2004), and high levels of electrostatic charges, resulting in increased interparticle cohesive forces and potentially leading to poor product performance (Brodka-Pfeiffer et al, 2003;Kaialy, 2016). Moreover, jet-milling is incompatible with thermally sensitive materials and may raise safety worries due to dust exposure during processing (Tong and Chow, 2006).…”

Drug release from E chemistry hypromellose tablets using the Bio-Dis USP type III apparatus: An evaluation of the effect of systematic agitation and ionic strength

“…It has been argued that collisions allow electrons trapped in high-energy states on one particle to transfer to the vacant low-energy states on another particle assuming that the surface density of trapped electrons is initially the same on all particles [50,51]. Therefore, as HPMC polymer is blended with theophylline, the charge that is measured is mainly that of the polymer despite the drug being in excess (by weight).…”

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

“…At low RH values, water will absorb (only) on the surface of particles promoting a decrease in interparticle adhesion forces due to a reduction in the electrostatic forces by charge dissipation [116,117]. But, at high RH values water will form a complete monolayer of water molecules on the surface of the crystalline solid particles [118], leading to increased interparticle adhesion forces due to increased specific capillary (liquid bridge) forces, which function as drug-carrier adhesion forces resulting in poor powder deaggregation (i.e.…”

“…Such tribocharging could have a considerable effect on the blending efficiency of adhesive mixtures [4,117,216]. Several studies related the blending homogeneity of adhesive mixtures for inhalation to an increased level in the overall net-charge [64,217,218].…”