Tribo-electric charging and adhesion of cellulose ethers and their mixtures with flurbiprofen

Abstract

The pervasiveness of tribo-electric charge during pharmaceutical processing can lead to the exacerbation of a range of problems including segregation, content heterogeneity and particle surface adhesion. The excipients, hydroxypropyl methylcellulose (HPMC) and methylcellulose (MC), are often used in drug delivery systems and so it is important to understand the impact of associated factors on their charging and adhesion mechanisms, however, little work has been reported in this area. Such phenomena become more prominent when excipients are introduced to a powder mixture alongside the active pharmaceutical ingredient(s) (APIs) with inter-and intra-particulate interactions giving rise to electrification and surface adhesion of powder particles. The aim of this study was to understand the impact of material attributes (particle size, hydroxypropoxyl (Hpo) to methoxyl (Meo) ratio and molecular size) on the charging and adhesion characteristics of cellulose ethers. Furthermore, a poorly compactible and highly electrostatically charged drug, flurbiprofen, was used to develop binary powder mixtures having different polymer to drug ratios and the relationship between tribo-electric charging and surface adhesion was studied. Charge was induced on powder particles and measured using a custom built device based on a shaking concept, consisting of a Faraday cup connected to an electrometer. The diversity in physicochemical properties has shown a significant impact on the tribo-electric charging and adhesion behaviour of MC and HPMC.Moreover, the adhesion and electrostatic charge of the API was significantly reduced when MC and HPMC were incorporated and tribo-electric charging showed a linear relationship (R 2 = 0.81-0.98) with particle surface adhesion, however, other factors were also involved. It is anticipated that such a reduction in charge and particle surface adhesion would improve flow and compaction properties during processing.

Triboelectrification: A review of experimental and mechanistic modeling approaches with a special focus on pharmaceutical powders

“…The electrostatic forces generated in such cases are a concern since the accumulated charge on these particles can cause segregation, adhesion or agglomeration leading to multiple manufacturing complications [15][16][17] . Electrostatic forces may also result in undesirable adhesion of charged drug particles to drug devices such as inhalers and can affect both the trajectory and the deposition of aerosols within the lungs 18 .…”

An assessment of triboelectrification effects on co-ground solid dispersions of carbamazepine

“…Triboelectrification has been used to study the impact of the counter ion on flurbiprofen salts as a consideration during the preformulation process [22], reduce the charging of flurbiprofen (a drug with a high propensity for charging) in binary mixtures of cellulose ethers [23], ordered mixing [24] and recently as a way of manipulating the charge of their final product of solid dispersions using single solvents and binary mixtures of solvents [25].…”

Tribo-electrification and Powder Adhesion Studies in the Development of Polymeric Hydrophilic Drug Matrices

“…However, hydrophilic derivatives of cellulose ethers, more specifically methylcellulose (MC) and hydroxypropyl methylcellulose (HPMC), are considered to be the main excipients of choice in the development of compressed hydrophilic matrix tablets [13,14]. Recently, tribo-electric charging behaviour of Methocel ® A4M, F4M, E4M, K4M, K15M and K100M, in plain and binary mixtures with the negatively charging API, flurbiprofen, have been studied [15]. The magnitude of the positive charge of the polymers, was distinct from the majority of other excipients previously reported, and was generally higher [9,15].…”

“…Recently, tribo-electric charging behaviour of Methocel ® A4M, F4M, E4M, K4M, K15M and K100M, in plain and binary mixtures with the negatively charging API, flurbiprofen, have been studied [15]. The magnitude of the positive charge of the polymers, was distinct from the majority of other excipients previously reported, and was generally higher [9,15]. Furthermore, it was reported that when highly charged flurbiprofen came into contact with Methocel ® , irrespective of its grade, it attached to its surface due to opposite polarities and the tribo-electric charge of the final powder mixture was significantly dissipated [15].…”