The Optimisation of Carrier Selection in Dry Powder Inhaler Formulation and the Role of Surface Energetics
Abstract
:1. Introduction
2. Lactose and Its Properties
2.1. Inhalation Grade Lactose
2.2. Challenges Associated with Carrier (Lactose)-Based DPI Formulations
3. Mechanism of API Detachment from Carrier
4. Carrier Factors Affecting Performance of DPI Formulations
4.1. Effect of Carrier Particle Size
4.2. Effect of Carrier Particle Shape and Surface Morphology
5. The Mixing Process
5.1. Mixing Mechanisms
5.1.1. Convection
5.1.2. Diffusion
5.1.3. Shear
6. Optimisation of DPI Formulation Dispersion by Carrier Surface Modification
6.1. Addition of Fine Lactose Particles
6.2. Use of Force Control Agents
7. Surface Energetics and Particle Interactions
7.1. Surface Energy Determination
7.2. Use of IGC in Measuring Surface Energetics
7.3. Use of Surface Energetics to Optimise and Control DPI Performance
8. Expert Opinion and Final Remarks
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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Title of Article and Author(s) | Focus of Review Article |
---|---|
The Influence of Fine Excipient Particles on the Performance of Carrier-Based Dry Powder Inhalation Formulations | Active site and agglomerate theories to explain the effect of lactose fines |
Jones and Price [48] | |
Particle Engineering for Pulmonary Drug Delivery | Surface morphology and dispersion behaviour in relation to asperities |
[49] | |
Formulation strategy and use of excipients in pulmonary drug delivery | Hydrophobic lubricants Carrier free formulations |
Pilcer and Amighi [5] | |
Lactose as a carrier for inhalation products: Breathing new life into an old carrier | Impact of lactose physicochemical properties such as size, size distribution, shape and surface roughness of the particle, the presence of moisture, impurities or performance |
Marriot and Frijlink [50] | |
A critical view on lactose-based drug formulation and device studies for dry powder inhalation: Which are relevant and what interactions to expect | Carrier surface properties and role in drug–carrier interaction in relation to active sites on the carrier surface Role of amorphous spots and carrier fines in drug–carrier interactions The need for balance between cohesive and adhesive forces in DPI formulations and forces required for dispersion during inhalation and how this balance relies on the control of interparticulate force Relationship between active sites and high surface energy |
de Boer, Chan [17] | |
Physico-chemical aspects of lactose for inhalation | Physicochemical properties of lactose that affect DPI performance, including carrier size, distribution and shape; surface roughness; polymorphic form of the carrier; flow properties and electrostatic charge |
Kou, Chan [25] | |
Drug–lactose binding aspects in adhesive mixtures: Controlling performance in dry powder inhaler formulations by altering lactose carrier surfaces | Engineering of lactose surface morphology through surface smoothness, surface roughness, solvent-based coating and mechanical dry coating Characterisation of coating quality |
Zhou and Morton [51] | |
Technological and practical challenges of dry powder inhalers and formulations | Briefly mentions the use of crystalline and sieved lactose fraction as carriers in DPIs and passivation of active sites on carriers by ball milling, wet smoothing and use of FCAs |
Hoppentocht, Hagedoorn [52] | |
A proposed definition of the ‘activity’ of surface sites on lactose carriers for dry powder inhalation | Relationship between carrier surface activity and the energy with which they bind APIs Preferential occupation of active sites and retaining of drug particles on active sites during drug dispersion |
Grasmeijer, Frijlink [53] | |
Formulation Design of Dry Powders for Inhalation | Improving dispersion by lactose fines and FCAs; effects of lactose size, shape and morphology in dispersion Preferential attachment of lactose fines to high energy sites, which occurs as a result of clefts, amorphous domains, different crystalline orientations or other surface defects related to moisture, charge or contamination on lactose surface |
Weers and Miller [54] | |
From single excipients to dual excipient platforms in dry powder inhaler products | The use of lactose as a single excipient platform in DPI formulations and the introduction of a functional additive (Mg stearate used as a lubricant, FCA, stabiliser, water barrier and chemical stabiliser) to form a dual excipient platform for DPIs |
Shur, Price [55] | |
A review of factors affecting electrostatic charging of and adhesive mixtures for inhalation | General review on the impact of electrostatics on Dpi formulations Influence of polymorphic form and size distribution of lactose on electrostatic charge, and how surface charge on carrier and drug can affect the dry coating or mixing process and Dpi aerosolisation |
Kaialy [56] | |
Influence of physical properties of carrier on the performance of dry powder inhalers | Impact of carrier properties on aerosolisation including carrier particle size (size distribution), shape, morphology (surface roughness), density and geometric diameter. Role of fine carrier and associated theories (active site, agglomeration, fluidisation theory and buffer hypothesis) |
Peng, Lin [3] | |
Modelling the performance of carrier-based dry powder inhalation formulations: Where are we, and how to get there? | More general carrier-based review, focused on the key performance determinants of DPI formulations Carrier size and size distribution, concentration and size of fine carrier, carrier surface roughness and porosity and carrier shape were identified as carrier components that affect DPI performance |
Elsayed and Shalash [57] |
DPI Enhancing Strategies | Rationale | References |
---|---|---|
Use of fine carrier particles as performance modulators | Active sites theory, Agglomerate theory | [26,58,59,60] |
Carrier surface roughening | Carrier nanopores reduce adhesion force by reducing effective contact area between carrier and drug particles, while carrier micropores facilitate deagglomeration of fine drug particles | [71,72,73] |
Carrier surface smoothening | Smoother surface increases surface contact area and reduces crevices where fine drug particles are tightly held to carrier particles | [60,71,74] |
Use of force control agents | Passivation of active sites on carrier particles/reduction in cohesive forces through selection of FCAs, e.g., MgSt and Leucine | [68,70,75] |
Polymers, e.g., PVP and Ethyl cellulose | [24] |
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Abiona, O.; Wyatt, D.; Koner, J.; Mohammed, A. The Optimisation of Carrier Selection in Dry Powder Inhaler Formulation and the Role of Surface Energetics. Biomedicines 2022, 10, 2707. https://doi.org/10.3390/biomedicines10112707
Abiona O, Wyatt D, Koner J, Mohammed A. The Optimisation of Carrier Selection in Dry Powder Inhaler Formulation and the Role of Surface Energetics. Biomedicines. 2022; 10(11):2707. https://doi.org/10.3390/biomedicines10112707
Chicago/Turabian StyleAbiona, Olaitan, David Wyatt, Jasdip Koner, and Afzal Mohammed. 2022. "The Optimisation of Carrier Selection in Dry Powder Inhaler Formulation and the Role of Surface Energetics" Biomedicines 10, no. 11: 2707. https://doi.org/10.3390/biomedicines10112707
APA StyleAbiona, O., Wyatt, D., Koner, J., & Mohammed, A. (2022). The Optimisation of Carrier Selection in Dry Powder Inhaler Formulation and the Role of Surface Energetics. Biomedicines, 10(11), 2707. https://doi.org/10.3390/biomedicines10112707