(267e) Investigation of Electrostatic Properties of Lactose Powders: Implications for Dry Powder Inhaler (DPI) Processes

Dry powder inhaler (DPI) products are designed to deliver a dry powder active ingredient to a patient’s lungs using an inhaler device. The formulation typically consists of a homogenous blend of the active ingredient and an excipient (typically lactose), which is contained within a reservoir, capsule, or blister. Such formulations are produced by physically mixing micronised drug particles and the larger-sized excipient ‘carrier’ particles. Contrary to many conventional tableting formulations, the excipient is an important functional ingredient in a DPI formulation. The excipient carrier plays at least two roles in the formulation. Since the active ingredient is used in very small quantities, blending with the excipient is necessary to enable delivery of such a small quantity. Second, the excipient must separate from the drug during inhalation so that the drug can be inhaled into the patient’s lungs.

The excipient physical properties and interfacial forces affect the blend uniformity and drug release of the DPI formulation. Some of these properties include particle size distribution, flowability, surface chemistry, morphology, and electrostatic properties of the excipient. It is important that these characteristics are controlled during manufacture and storage of the excipient. The main challenges in DPI development are producing a uniform blend for accurate dosing and then proper drug separation during inhalation. Beyond that, reducing batch to batch variability is extremely challenging in these types of formulations.

Electrostatic charges of the excipient and drug particles (API) can affect the performance of dry powder inhalation drug formulations. Electrostatic forces on the excipient could cause the API particle to adhere to the surface of the excipient and prevent release. Also, electrostatic forces in the final blend could affect the powders release from the device. Of course, variability in charge profiles could cause variability in the final drug fine particle fraction (API that would be released to the patient). Characterization of these charges is an important tool to possibly allow a higher percentage of the API to be released from the excipient/device. Managing or controlling these charges could also be important to reduce the variability of API release. However, due to the complexity of the mechanisms at the origin of triboelectric effects, electrostatics has been only recently investigated for pharmaceutical powders [1,2].

In this study, the electrostatic properties of lactose excipients designed for DPI applications (AeroFlo, Kerry) have been investigated with the GranuCharge (GranuTools)[3]. Anhydrous and monohydrate powders differing from their particle size distribution have been selected. Moisture is controlled by conditioning the powders before the measurements at a fixed relative humidity with a specifically designed rotating tumbler coupled with a humid air generator (GranuMidity, Granutools). Then, powder charge density is measured before and after the powder flow through a Stainless Steel SS316L pipe. During the flow, the particle/particle and particle/pipe interactions lead to a charge buildup due to triboelectric effect, increasing the overall charge density of the powder. The selected powders can then be classified according to their sensibility to tribocharging. We show how the micro properties of the grains as well as the nature of the cohesive interactions drastically influence the charge buildup during the flow. Furthermore, the influence of moisture inside the powder on its electrostatic behaviour is also highlighted. The results give useful insights that will help improving post-manufacturing conditioning of the excipient and/or drug formulation to help to reduce the charge buildup and charge variability.

[1] C. Allenspach, P. Timmins, G. Lumay, J. Holman, T. Minko, International Journal of Pharmaceutics, 596, 2021.

[2] A. Rescaglio, J. Schockmel, F. Francqui, N. Vandewalle, G. Lumay, ANNUAL TRANSACTIONS OF THE NORDIC RHEOLOGY SOCIETY, 25, 2017.

[3] G. Lumay, S. Pillitteri, M. Marck, F. Monsuur, T. Pauly, Q. Ribeyre, F. Francqui, N. Vandewalle, Journal of Drug Delivery Science and Technology, 53, 2019.