Dry Powder Inhalation System Research Articles

Stability test of novel combined formulated dry powder inhalation system containing antibiotic: physical characterization and in vitro–in silico lung deposition results

Objective: The aim was to study the stability of dry powder inhaler (DPI) formulations containing antibiotic with different preparation ways – carrier-based, carrier-free, and novel combined formulation – and thereby to compare their physicochemical and in vitro–in silico aerodynamical properties before and after storage. Presenting a novel combined technology in the field of DPI formulation including the carrier-based and carrier-free methods, it is the most important reason to introduce this stable formulation for the further development of DPIs.Methods: The structure, the residual solvent content, the interparticle interactions, the particle size distribution and the morphology of the samples were studied. The aerodynamic values were determined based on the cascade impactor in vitro lung model. We tested the in silico behavior of the novel combined formulated samples before and during storage.Results: The physical measurements showed that the novel combined formulated sample was the most favorable. It was found that thanks to the formulation technique and the use of magnesium stearate (MgSt) has a beneficial effect on the stability compared with the carrier-based formulation without MgSt and carrier-free formulations. The results of in vitro and in silico lung models were consistent with the physical results, so the highest deposition was found for the novel combined formulated sample during the storage.Conclusions: It can be established that after the storage a novel combined formulated DPI contained amorphous drug to have around 2.5 μm mass median aerodynamic diameter and nearly 50% fine particle fraction predicted high lung deposition in silico also.

Numerical investigation of deposition mechanism in three mouth–throat models

Understanding the deposition mechanisms of pharmaceutical aerosol in the mouth-throat (MT) is crucial to developing an in vitro method which aims to better predict in vivo lung deposition. This paper investigated the effect of geometrical variation, particle size and airflow rate on the fine particle deposition in the US pharmacopeia throat (USP), idealized mouth-throat (IMT) and realistic mouth-throat (RMT) models. The flow-field equations were solved with the SST model by computational fluid dynamics (CFD) and monodispersed particles in the size range of 1–30 μm were tracked with discrete phase method (DPM). The results indicated that the deposition fraction and spatial distribution were highly sensitive to the geometrical variation and respiratory conditions such as the inhalation airflow rate and particle size. Moreover, the effect of geometrical variation on the particle escape pattern was more dominant. Comparing to the IMT model, more uniformly distribution of escape particles was observed at the outlet of RMT. While the total deposition fractions in IMT and RMT were similar, the spatial distributions of deposited particles were significantly different. In the RMT model, fewer particles were deposited in mouth and trachea, but the depositions in the pharyngeal and laryngeal regions were more uniform. These conclusions could help study the in vitro-in vivo correlation of dry powder inhaler systems.

Preparation and Characterization of Celecoxib Agglomerated Nanocrystals and Dry Powder Inhalation Formulations to Improve its Aerosolization Performance

Background: Celecoxib is a non-steroidal anti-inflammatory drug used extensively in the treatment of pain, arthritis, and cancers. However, its administration is limited due to its several disadvantages including gastric irritation and hepatic first pass metabolism. Among numerous methods for pulmonary drug delivery, dry powder inhalation systems show the promising approach to be used as alternative routes for oral drug delivery. This study was conducted to develop agglomerated nanocrystals and carrier-free Celecoxib dry powder inhalation formulation for pulmonary delivery in lung cancer treatment. Methods: Spray dried Celecoxib, Celecoxib nanocrystals, and agglomerated nanocrystals were characterized in the case of particle size distribution, crystallinity, and aerosolization efficiency including mass median aerodynamic diameter (MMAD), fine particle fraction (FPF), and geometric standard deviation (GSD) by Next Generation Impactor (NGI). Results: Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analyses showed the lack of any interaction and polymorphism in the prepared formulations. Results showed that the optimized spray-dried formulation of Celecoxib was in the appropriate size range, and shape for pulmonary delivery. MMAD, FPF, and GSD values for spray-dried formulation were 31.93±3.93%, 4.82±0.21 µm, and 1.81±0.05, respectively. Conclusion: Although the agglomerated nanocrystals of Celecoxib showed comparable aerosolization efficiency indexes with carrier free spray-dried Celecoxib formulation, further investigations are necessary to optimize the agglomeration process to obtain agglomerated nanocrystals of Celecoxib with improved aerosolization efficiency indexes.

Dry powder inhaler for pulmonary drug delivery: human respiratory system, approved products and therapeutic equivalence guideline

Pulmonary drug delivery is the promising delivery route to treat not only respiratory diseases but also systemic diseases and has proven as a potential delivery route for complex drugs that cannot be delivered orally. Development of dry powder inhalation systems targets the delivery of fine drug particles to the deep lung surface by a combination of particle deposition and clearance in human respiratory tract. Various dry powder inhalers (DPIs) with their advanced technologies have been proposed and marketed to treat pulmonary diseases such as asthma, chronic obstructive pulmonary diseases, cystic fibrosis and furthermore, systemic diseases such as diabetes and schizophrenia. Bioequivalent therapeutic effects can be derived from generic products that provide additional benefits to the patients and the health care system. Currently, European Medicines Agency (EMA) have established the bioequivalent methods to develop and approve the inhaled products. This review covers the anatomical and physiological characteristics of human respiratory tract to understand the mechanism of drug deposition and clearance. Also, therapeutic areas for both local and systemic treatment, DPI products and their advanced technologies are presented. Finally, European Medicines Agency (EMA) guidelines for inhaled products are presented to demonstrate the therapeutic bioequivalence between generic and reference products.

Physicochemical stability and aerosolization performance of dry powder inhalation system containing ciprofloxacin hydrochloride

Antibiotic delivery in form of dry powder inhalation has been studied for possible clinical treatment of respiratory tract infection in the recent years. Dry powder inhalation of ciprofloxacin hydrochloride (CIP) assures local antibacterial activity and comfort of easy application. The aim of this work was to test the stability of co-spray-dried CIP in carrier free system. Since the microparticles in the dry powder system are amorphous and do not contain any stabilizer, the effects of temperature and relative humidity (RH) on the physicochemical properties and aerosolization behavior are very important. Therefore investigation of the role of excipients (such as polyvinyl alcohol (PVA), l-leucine (LEU) and hydroxypropyl-beta-cyclodextrin (CD)) on physicochemical stability and aerosolization performance is essential element prior designing the final dosage form. Stability tests (stress and accelerated) were performed at 40±2°C and 75±5% RH during 6 months. Particle characterization and size measurement – as the most important parameters in aerodynamic behavior – were done by the laser diffraction method, the surface morphology of microparticles was evaluated by scanning electron microscopy (SEM). The physiochemical properties of microparticles were investigated by X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC). The resulting aerodynamic behavior of microparticles was studied by Andersen cascade impactor. The overall stability results (against RH and temperature) showed that microparticles containing CIP and LEU alone and in combination with the other excipients were more stable than those containing PVA or CD alone. In relation to fine particle fraction and mass median aerodynamic diameter (determining the aerosolization parameters), it was found that the particle size and particle shape did not show significant changes after the storage.Among the excipients LEU was found to have many advantages, including relatively simple formulation, enhanced aerosolization behaviour, convenient portability and inherently improved stability. Such a composition may serve as an innovative drug delivery system for the local treatment of respiratory tract infection and cystic fibrosis.

Formulation of novel dry powder inhalation for fluticasone propionate and salmeterol xinafoate with capsule-based device

The aim of this study was to develop a novel fluticasone propionate (FP) and salmeterol xinafoate (SX)-loaded dry powder inhaler (DPI) system, which was composed of powder formulation and performance. The air flow resistances were determined with various types of DPI device, showing that the modified RS01 device gave the specific resistance similar to the commercial DPI device. The particle properties of FP, SX, and inhalation grade lactose particles, such as particle size, size distribution, and fine content, were assessed. Subsequently, the aerodynamic behaviors of the DPI powder formulations were evaluated by the in vitro deposition of drugs in the DPI products using Andersen cascade impactor. Amongst the DPI powder formulations tested, the formulation composed of FP, SX, Respitose® SV003, Respitose® SV010, and Respitose® ML006 at the weight ratio of 0.5/0.145/19/19/2 gave depositions, emitted dose, fine particle dose, fine particle fraction, and mass median aerodynamic diameter of drugs similar to the commercial product, suggesting that they had similar aerodynamic behaviors. Furthermore, it gave excellent content uniformity. Thus, this DPI using the modified RS01 device would be recommended as a candidate for FP and SX-loaded pharmaceutical DPI products.

Recent advances in capsule-based dry powder inhaler technology

Pulmonary drug delivery is currently the focus of accelerated research and development because of the potential to produce maximum therapeutic benefit to patients by directly targeting drug to the site of pathology in the lungs. Among the available delivery options, the dry powder inhaler (DPI) is the preferred device for the treatment of an increasingly diverse range of diseases. However, because drug delivery from a DPI involves a complex interaction between the device and the patient, the engineering development of this medical technology is proving to be a great challenge. Development of DPI systems that target the delivery of fine drug particles to the deeper airways in the lungs using a combination of improved drug formulations and enhanced delivery device technologies means that each of these factors contributes to overall performance of the aerosol system. There are a large range of devices that are currently available, or under development, for clinical use, however no individual device shows superior clinical efficacy. A major concern that is very relevant in day-to-day clinical practice is the inter- and intra-patient variability of the drug dosage delivered to the deep lungs from the inhalation devices, where the extent of variability depends on the drug formulation, the device design, and the patient’s inhalation profile. This variability may result in under-dosing of drug to the patient and potential loss of pharmacological efficacy. This article reviews recent advances in capsule-based DPI technology and the introduction of the ‘disposable’ DPI device.

CFD-DEM study of the aerosolisation mechanism of carrier-based formulations with high drug loadings

Understanding the aerosolisation mechanism of carrier-based formulation with high drug loadings is crucial to developing high-dose dry powder inhalers. This paper investigated the effect of carrier-drug mass ratio in different conditions based on the combined computational fluid dynamics (CFD) and discrete element method (DEM) approach, aiming to develop better understanding of the aerosolisation mechanism of carrier-based formulation with high drug loadings. The carrier-based formulations composed of drug (salbutamol sulphate) and carrier (polystyrene bead) were formed with varied carrier-drug mass ratios ranging from 5:1 to 25:1. The aerosolisation process after impaction with a target wall was simulated and focuses mainly on the effects of four variables: carrier size, air flow velocities, impact velocities and impact angles. Dynamics of impact process and post-impact analysis were discussed. The fine particle fractions (FPFs), the amount of fine particles below 5μm in the aerosol, were measured to characterise the aerosolisation performance. The results showed that increasing the carrier-drug mass ratio will improved the aerosolisation performance. The influencing degree of carrier-drug mass ratio on aerosol performance was dependent on the carrier size. For a larger carrier with a high carrier-drug ratio corresponding to high surface coverage, the airflow velocity, impact velocity and angle have only a minor effect on the aerosolisation performance. The best solution was to use the smaller carriers to replace the larger ones if the requirements of drug loading and FPFs need to be satisfied at the same time. These conclusions could be used to help design the optimal carrier-drug mass ratio formulations for different carrier-based dry powder inhaler systems.

New aspects of developing a dry powder inhalation formulation applying the quality-by-design approach

The current work outlines the application of an up-to-date and regulatory-based pharmaceutical quality management method, applied as a new development concept in the process of formulating dry powder inhalation systems (DPIs). According to the Quality by Design (QbD) methodology and Risk Assessment (RA) thinking, a mannitol based co-spray dried formula was produced as a model dosage form with meloxicam as the model active agent.The concept and the elements of the QbD approach (regarding its systemic, scientific, risk-based, holistic, and proactive nature with defined steps for pharmaceutical development), as well as the experimental drug formulation (including the technological parameters assessed and the methods and processes applied) are described in the current paper.Findings of the QbD based theoretical prediction and the results of the experimental development are compared and presented. Characteristics of the developed end-product were in correlation with the predictions, and all data were confirmed by the relevant results of the in vitro investigations. These results support the importance of using the QbD approach in new drug formulation, and prove its good usability in the early development process of DPIs. This innovative formulation technology and product appear to have a great potential in pulmonary drug delivery.

The use of freeze-dried mannitol to enhance the in vitro aerosolization behaviour of budesonide from the Aerolizer®

The efficiency of drug delivery from drug-carrier dry powder inhaler (DPI) systems is typically low. The purpose of this study was to examine the aerosolization performance of a hydrophobic drug, budesonide (BUD), from DPI formulations containing a promising carrier, freeze-dried mannitol (FDM), and to compare the results to those obtained previously with a hydrophilic drug, salbutamol sulphate (SS).The results showed that, in comparison to the formulation containing commercial BUD and commercial lactose, a total of 3.8-fold increase in the fine particle fraction (FPF) was obtained from the formulation containing FDM (FPF: 7.5% versus 29%) whereas a total of 4.6-fold increase in the FPF was obtained from the formulation containing FDM and leucine additive (FPF: 35%). Regression analysis showed DPI formulations containing carrier particles with a more elongated/less spherical shape, a higher content of fine particulates (<5μm) and a higher porosity to produce higher FPFs of BUD.FDM promoted the aerosolization of budesonide intended for pulmonary delivery. The addition of leucine (by 4.8%, w/w) has further improved the flow and the aerosolization properties of FDM. FDM produced higher aerodynamic diameters and smaller FPFs of BUD as compared to SS, attributable to BUD having a higher electrostatic charge density and a higher agglomeration tendency than SS.

Development and Evaluation of Chitosan Microparticles Based Dry Powder Inhalation Formulations of Rifampicin and Rifabutin.

The lung is the primary entry site and target for Mycobacterium tuberculosis; more than 80% of the cases reported worldwide are of pulmonary tuberculosis. Hence, direct delivery of anti-tubercular drugs to the lung would be beneficial in reducing both, the dose required, as well as the duration of therapy for pulmonary tuberculosis. In the present study, microsphere-based dry powder inhalation systems of the anti-tubercular drugs, rifampicin and rifabutin, were developed and evaluated, with a view to achieve localized and targeted delivery of these drugs to the lung. The drug-loaded chitosan microparticles were prepared by an ionic gelation method, followed by spray-drying to obtain respirable particles. The microparticles were evaluated for particle size and drug release. The drug-loaded microparticles were then adsorbed onto an inhalable lactose carrier and characterized for in vitro lung deposition on an Andersen Cascade Impactor (ACI) followed by in vitro uptake study in U937 human macrophage cell lines. In vivo toxicity of the developed formulations was evaluated using Sprague Dawley rats. Both rifampicin and rifabutin-loaded microparticles had MMAD close to 5 μm and FPF values of 21.46% and 29.97%, respectively. In vitro release study in simulated lung fluid pH 7.4 showed sustained release for 12 hours for rifampicin microparticles and up to 96 hours for rifabutin microparticles, the release being dependent on both swelling of the polymer and solubility of the drugs in the dissolution medium. In vitro uptake studies in U937 human macrophage cell line suggested that microparticles were internalized within the macrophages. In vivo acute toxicity study of the microparticles in Sprague Dawley rats revealed no significant evidence for local adverse effects. Thus, spray-dried microparticles of the anti-tubercular drugs, rifampicin and rifabutin, could prove to be an improved, targeted, and efficient system for treatment of tuberculosis.

An Investigation into the Powder Release Behavior from Capsule-Based Dry Powder Inhalers

A methodology for studying the deagglomeration performance and emptying behavior of micronized mannitol powder from two commercial capsule-based dry powder inhalers (DPIs), the low- and high-resistance RS01®, is presented. Mathematical modeling played a key role in the interpretation of the powder release behavior from these two DPI systems. Non-linear regression models, which were characterized from the aerosol obscuration versus time profiles obtained from laser diffraction particle sizing data, were used to estimate rate constants for emptying of mannitol powder. The effects of device resistance and associated pressure drops, sampling flow rate, rates of powder emptying, and the presence of capsule on the dispersion characteristics were studied. The presence of a capsule significantly improved the aerosolization performance of mannitol powder from both inhalers, which may be due to the extended powder–air–device interactions within the device. It is important to consider the stochastic nature of moveme...

Therapeutic Efficacy of Stable Analogues of Vasoactive Intestinal Peptide against Pathogens

Vasoactive intestinal peptide (VIP) is an anti-inflammatory neuropeptide recently identified as a potential antimicrobial peptide. To overcome the metabolic limitations of VIP, we modified the native peptide sequence and generated two stable synthetic analogues (VIP51 and VIP51(6-30)) with better antimicrobial profiles. Herein we investigate the effects of both VIP analogues on cell viability, membrane integrity, and ultrastructure of various bacterial strains and Leishmania species. We found that the two VIP derivatives kill various non-pathogenic and pathogenic Gram-positive and Gram-negative bacteria as well as the parasite Leishmania major through a mechanism that depends on the interaction with certain components of the microbial surface, the formation of pores, and the disruption of the surface membrane. The cytotoxicity of the VIP derivatives is specific for pathogens, because they do not affect the viability of mammalian cells. Docking simulations indicate that the chemical changes made in the analogues are critical to increase their antimicrobial activities. Consequently, we found that the native VIP is less potent as an antibacterial and fails as a leishmanicidal. Noteworthy from a therapeutic point of view is that treatment with both derivatives increases the survival and reduces bacterial load and inflammation in mice with polymicrobial sepsis. Moreover, treatment with VIP51(6-30) is very effective at reducing lesion size and parasite burden in a model of cutaneous leishmaniasis. These results indicate that the VIP analogues emerge as attractive alternatives for treating drug-resistant infectious diseases and provide key insights into a rational design of novel agents against these pathogens.

Treating mannitol in a saturated solution of mannitol: A novel approach to modify mannitol crystals for improved drug delivery to the lungs

The aim of this study was to evaluate the influence of treatment of a promising dry powder aerosol carrier (mannitol) on the aerosolization performance of salbutamol sulphate (SS) using a novel approach: treating excess commercial carrier particles in a saturated solution of the same carrier. Commercial mannitol (CM) particles were treated with aqueous mannitol supersaturated solutions (20% and 25% w/v), under stirring, (300 rpm) for either 24h or 48 h. The results showed that particle treatment did not alter the polymorphic form of mannitol (β-mannitol); however, all treated mannitol particles demonstrated smoother surface topography and improved aerosolization performance compared to CM in dry powder inhalations. Unlike the concentration of mannitol solution used during treatment, the time of treatment to collect mannitol crystals was an essential key to modify the physical properties of mannitol and its effect on the aerosolization performance. In comparison to mannitol particles treated for 48 h, mannitol particles treated for 24h demonstrated larger size, more elongated-less regular shape, and smoother surfaces. No apparent relationship was obtained between in vitro aerosolisation behavior of SS with either mannitol particle size or shape descriptors. However, despite their larger size and more irregular-less uniformed shape, treated mannitol particles with smoother surfaces generated drug particles with smaller aerodynamic size and are expected to deliver higher amounts of drug to lower airways. The results demonstrated the potential of treating mannitol particles in aqueous solutions of the same material under controlled conditions to produce mannitol particles promising for dry powder inhaler systems. The results suggested that mannitol particle surface texture properties dominate over both particle size and particle shape of mannitol in terms of determining the aerosolization performance of mannitol.

Strategic Formulation Study on Dry Powder Inhalation System Based on Modulated Molecular Properties and Controlled Pharmacokinetics

Cyclosporine A (CsA) has been widely used as an immunosuppressive agent, and recent outcomes from clinical studies are indicative of the potent therapeutic potential of CsA for chronic asthma and airway inflammation. The clinical use of CsA for airway inflammatory diseases is partly limited because of low oral bioavailability and severe systemic side effects. A number of CsA dosage forms have been proposed to overcome these drawbacks, for example, nebulizer formulation and metered-dose inhaler formulation for inhalation therapy, whereas these liquid formulations sometimes contain organic solvents and other solubilizers, leading to local irritant potency. In this context, our group developed a dry powder inhalation (DPI) system of CsA, employing a polymer-based amorphous solid dispersion (ASD) approach, for inhalation therapy on airway inflammations. There was marked improvement in dissolution behavior of the ASD formulation compared with that of an amorphous CsA. The new DPI system of CsA exhibited high dispersibility and suitable particle distribution for inhalation therapy. In vivo experiments demonstrated that inhaled DPI system of CsA attenuated inflammatory events in experimental asthma/chronic obstructive pulmonary disease (COPD) model rats as evidenced by a decrease of infiltrated granulocytes, and there was no excessive increase in systemic exposure of CsA at a pharmacologically effective dose, possibly leading to reduced systemic side effects. From these findings, combination use of CsA-loaded ASD and DPI systems might be a promising approach for the treatment of airway inflammatory diseases with improved pharmacodynamics and lower systemic exposure.

Rational design of a dry powder inhaler: device design and optimisation

As part of the development of a dry powder inhalation system for the treatment of asthma and chronic obstructive pulmonary disease, this work specifically aimed at the systematic, however, cost-effective and efficient development of an inhalation device. Based on theoretical design considerations and an initial inhaler prototype, the concept of a modular inhaler was developed. The modular inhaler was used for the systematic evaluation of the influence of the inhaler's inner dimensions on the resistance to the air flow and the in-vitro deposition characteristics of the inhalation system by using statistical design of experiments and cascade impaction analysis. A reliable statistical model enabled the accurate prediction of the device resistance of any combination of inner dimensions of the inhaler. In conjunction with results from in-vitro deposition studies, this allowed for the definition of optimised inner dimensions of the inhaler to maximise the fine particle fraction and minimise oropharyngeal deposition within the desired range of the inhaler's resistance to air flow. The concept of the modular inhaler and statistical design and evaluation of experiments proved to be important tools for an efficient and successful product development. Eventually, the approaches described and the knowledge obtained enabled the cost-effective development and design of a technically feasible and competitive dry powder inhaler.

Micronized drug powders in binary mixtures and the effect of physical properties on aerosolization from combination drug dry powder inhalers

Objectives: To evaluate physicochemical properties of two micronized drugs, salbutamol sulfate (SS) and beclomethasone dipropionate (BDP) prepared as dry powder inhalation physical blends. Methods: Five different blends of SS:BDP ratios of 0:100, 25:75, 50:50, 75:25, and 100:0 (w/w) were prepared. Aerosolization performance was evaluated using a multistage impinger and a Rotahaler® device. Results: The median SS particle diameter was larger than BDP (4.33 ± 0.37 µm compared to 2.99 ± 0.15 µm, respectively). The SS appeared to have a ribbon-like morphology, while BDP particles had plate-like shape with higher cohesion than SS. This was reflected in the aerosolization performance of the two drugs alone, where SS had a significantly higher fine particle fraction (FPF) than BDP (12.3%, 3.1% and 2.9%, 0.2%, respectively). The study of cohesion versus adhesion for a series of SS and BDP probes on SS and BDP substrates suggested both to be moderately adhesive, verified using scanning Raman microscopy, where a physical association between the two was observed. A plot of loaded versus emitted dose indicated that powder bed fluidization was significantly different when the drugs were tested individually. Furthermore, the FPF of the two drugs from the binary blends, at all three ratios, were similar. Conclusions: Such observations indicate that when these two drugs are formulated as a binary system, the resulting powder structure is altered and the aerosolization performance of each drug is not reflective of the individual drug performance. Such factors could have important implications and should be considered when developing combination dry powder inhalation systems.

Development of Dry Powder Inhalation System for Therapeutic Peptides Based on Modulated Molecular Properties and Controlled Pharmacokinetics

Development of Dry Powder Inhalation System for Therapeutic Peptides Based on Modulated Molecular Properties and Controlled Pharmacokinetics

Development of chitosan-based dry powder inhalation system of cisplatin for lung cancer

Cisplatin, a platinum compound, exerts its cytotoxic effects by coordinating to DNA where it inhibits both replication and transcription, and induces programmed cell death. It is used in the treatment of non-small cell lung cancer. In the present study, an attempt was made to achieve better treatment of lung cancer by direct lung delivery of cisplatin microparticulate systems, which helps to localize the drug in the lungs, and also provide sustained action. Cisplatin-loaded chitosan microspheres were prepared by emulsification and ionotropic gelation method, and characterized for drug content, particle size, densities, flow properties, moisture content, and surface topography by SEM and in vitro drug release was evaluated in simulated lung fluid at 37° at pH 7.4. The respirable or fine particle fraction (FPF) was determined by using twin stage impinger (TSI). Further stability evaluation of cisplatin-loaded DPI systems was carried out at 25°/60% RH and at 40°/75% RH.

The influence of drug loading on formulation structure and aerosol performance in carrier based dry powder inhalers

Previous studies have reported that carrier:drug ratio and carrier size influence the aerosol performance of dry powder inhalation systems. These previous studies were complicated by the heterogeneous nature of the carriers used, making it difficult to define an explicit relationship between parameters and performance. Here, the authors studied the influence of drug loading and carrier size on drug aerosol performance using homogeneous spherical model carriers. Different formulations containing drug (salbutamol sulphate) and carriers (polystyrene beads with median diameters of 82.8 μm, 277.5 μm and 582.9 μm, respectively) were prepared by varying the ratio of carrier to drug (from ∼5:1 to ∼85:1). The surface morphology of the carrier particles and force of adhesion were investigated using atomic force microscopy, while the aerosol performance was evaluated using a multi-stage liquid impinger. The carrier surface morphology for all carrier sizes was homogenous with root-mean square roughness values ≤112 nm. No significant difference in the force of adhesion between salbutamol sulphate and the three carrier sizes was observed. Significant differences in aerosol performance of salbutamol sulphate (measured as fine particle dose (FPD) and fraction (FPF) ≤ 5 μm) from the carriers were observed. Specifically, as carrier size increased FPF decreased. In comparison, as drug loading increased there was no change in FPF until a critical threshold was exceeded. Such observations suggest that: (A) aerosolisation performance is governed by carrier collisions and (B) when homogeneous carriers are used, the aerosol performance remains constant with respect to drug concentration, until the formulation transitions from an ordered mix to an agglomerated and/or segregated powder bed.