Performance Of Dry Powder Inhalers Research Articles

Investigation on the influence of design features on the performance of dry powder inhalers: Spiral channel, mouthpiece dimension, and gas inlet

As inhaler design is rarely studied but critically important in pulmonary drug delivery, this study investigated the influence of inhaler designs, including a novel spiral channel, mouthpiece dimensions (diameter and length) as well as gas inlet. Experimental dispersion of a carrier-based formulation in conjugation with computational fluid dynamics (CFD) analysis, was performed to determine how the designs affect inhaler performance. Results reveal that inhalers with a narrow spiral channel could effectively increase drug-carrier detachment by introducing high velocity and strong turbulent flow in the mouthpiece, although the drug retention in the device is significantly high. It is also found that reducing mouthpiece diameter and gas inlet size could greatly improve the fine particle dose delivered to the lungs, whereas the mouthpiece length plays a trivial influence on the aerosolization performance. This study contributes toward a better understanding of inhaler designs as relevant to overall inhaler performance, and sheds light on how the designs affect device performance.

Swirling flow and capillary diameter effect on the performance of an active dry powder inhalers

For patients with lung disease, dry powder inhalers (DPI) are profoundly beneficial. The current study introduces and develops a series of dry powder inhalers (DPIs). A capsule-based (size 0) active DPI was considered. The study aims to investigate whether swirling flow and outlet capillary diameter (dc_out) affect the percentage of emitted doses (ED) released from the capsule. Spiral vanes were added to the capillary inlet to produce a swirling flow. Computational fluid dynamics (CFD) was applied to simulate the problem. The results were compared with previous in vitro and numerical studies to validate the results. Based on the derived results, the small swirl parameter (SP) enhances the secondary flow and recirculation zone. It increases the central jet flow, which increases the ED value by about 5–20% compared to no-swirl flow. However, as the airflow rate increases, the recirculation zone enlarges, vorticities become dominant, and asymmetrical flow patterns emerge. Consequently, ED % drops significantly (more than 50%). As dc_out decreases, the vorticities around the outlet capillary become more potent, which is undesirable. Indeed, the emptying of the capsule does not happen ideally. The research provides a perspective on the device's design and DPI performance.

Surface Modification of lactose carrier particles using a fluid bed coater to improve fine particle fraction for dry powder inhalers

Surface roughness of carrier particles can impact dry powder inhaler (DPI) performance. There are opposing views on the effect of roughness on DPI performance. Hence, a systematic approach is needed to modify carrier surfaces and evaluate the impact on drug delivery. Carrier particle surfaces were modified by fluid bed coating with saturated lactose containing micronized lactose of different sizes (2, 5 and 8 μm) and coated to different levels (20, 40, 60 and 80%). Their drug delivery performance was assessed by the fine particle fraction (FPF). Roughness parameters, mean arithmetic roughness (Ra) and arithmetic mean height (Sa), of the carrier particles, were also evaluated using optical profilometry and scanning laser microscopy. Generally, particles of higher Ra had higher FPF. Higher Sa resulted in higher FPF only for particles with 60 and 80% coat levels. Reduced contact surface area between the drug particle and rougher carrier particle resulted in easier drug detachment during aerosolization. The 5 µm micronized lactose produced optimal carrier particles with respect to FPF and surface roughness. The study highlighted that with the ideal particles for surface roughening and coating level, surface roughening could be efficiently achieved by fluid bed coating for superior DPI performance.

Advancements in the Design and Development of Dry Powder Inhalers and Potential Implications for Generic Development.

Dry powder inhalers (DPIs) are drug-device combination products where the complexity of the formulation, its interaction with the device, and input from users play important roles in the drug delivery. As the landscape of DPI products advances with new powder formulations and novel device designs, understanding how these advancements impact performance can aid in developing generics that are therapeutically equivalent to the reference listed drug (RLD) products. This review details the current understanding of the formulation and device related principles driving DPI performance, past and present research efforts to characterize these performance factors, and the implications that advances in formulation and device design may present for evaluating bioequivalence (BE) for generic development.

The effects of grid design on the performance of 3D-printed dry powder inhalers

The grid structure is an indispensable part of most dry powder inhalers, but the effects of grid geometry on inhaler performance are rarely reported. This study aims to systemically investigate the influence of grid design on the aerosolization performance of capsule-based inhalers through experiments and computational analysis. In-vitro aerosolization and deposition performance of commercial and 3D-printed customized inhalers with different grid mesh designs were experimentally studied using a Next Generation Impactor (NGI). Flow fields in the inhalers were generated, and average turbulence kinetic energy (TKE) and airstream trajectories were obtained through Computational Fluid Dynamics (CFD) analysis, delineating the effects of the different grid designs. Comparative studies using the commercial inhalers and the 3D-printed inhalers show a slightly better performance for the latter, probably due to the different materials used for the inhalers, confirming the suitability of 3D printing. Experimental results show that intensive grid meshes with a relatively small aperture size are beneficial to enhancing inhaler performance. Computational results illustrate that the intensive grid meshes can reduce vortexed airstreams and increase turbulent kinetic energy at the grids in general, which also supports the experimental results. In summary, inhalers with intensive grid meshes are preferred for capsule-based inhalers to enhance aerosolization performance. These findings have significant implications for the comprehensive understanding of how grid designs influence inhaler performance.

Validation of a cell integrated next-generation impactor to assess in vitro drug transport of physiologically relevant aerosolised particles

The development of novel inhaled formulations in the pre-clinical stage has been impeded by a lack of meaningful information related to drug dissolution and transport at the lung epithelia due to the absence of physiologically relevant in vitro respiratory models. The objective of the present study was to develop an in vitro experimental model, which combined the next generation impactor (NGI) and two respiratory epithelial cell lines, for examining the aerodynamic performance of dry powder inhalers and the fate of aerosolised drugs following lung deposition. The NGI impaction plates of stage 3 (i.e., a cut-off diameter of 2.82–4.46 µm) and stage 7 (i.e., a cut-off diameter of 0.34–0.55 µm) were modified to accommodate 3 cell cultures inserts. Specifically, Calu-3 cells and H441 cells, which are representative of the bronchial and alveolar epithelia in the lung, respectively, were cultivated at the air–liquid interface on SnapwellsTM with polycarbonate membranes. The aerodynamic particle size distribution of the modified NGI was investigated using resveratrol dry powder formulation (as a model drug). The suitability of such an in vitro model was confirmed by examining the in vitro aerodynamic performance of the model drug as compared to the conventional NGI setup (i.e., without the integrated Snapwell inserts), as well as the effect of experimental conditions (e.g., 60 L/min airflows) on the cells in the integrated Snapwell inserts. After deposition of the aerodynamically fractioned resveratrol, the permeation of the drug across the cell layer to the basolateral chamber of the Snapwell inserts was evaluated over 24 h. Results obtained from the drug transport study showed that the cell-integrated NGI provided realistic drug delivery conditions to the cells that can be used to assess the fate of fractionated aerosol particles. This system enables a better understanding of the in vitro drug deposition in the lungs and allows studies on both aerodynamic characterisation and drug transport (drug biological interactions with the cells) to be performed simultaneously.

Dry Powder Inhalers Based on Chitosan-Mannitol Binary Carriers: Effect of the Powder Properties on the Aerosolization Performance.

Carriers play an important role in improving the aerosolization performance of dry powder inhalers (DPIs). Despite that intensive attention had been paid to the establishment of the advanced carriers with controllable physicochemical properties in recent years, the design and optimization of carrier-based DPIs remain an empiricism-based process. DPIs are a powder system of complex multiphase, and thus their physicochemical properties cannot fully explain the powder behavior. A comprehensive exposition of powder properties is demanded to build a bridge between the physicochemical properties of carriers and the aerosolization performance of DPIs. In this study, an FT-4 powder rheometer was employed to explore the powder properties, including dynamic flow energy, aeration, and permeability of the chitosan-mannitol binary carriers (CMBCs). CMBCs were self-designed as an advanced carrier with controllable surface roughness to obtain enhanced aerosolization performance. The specific mechanism of CMBCs to enhance the aerosolization performance of DPIs was elaborated based on the theory of pulmonary delivery processes by introducing powder properties. The results exhibited that CMBCs with appropriate surface roughness had lower special energy, lower aeration energy, and higher permeability. It could be predicted that CMBC-based DPIs had greater tendency to fluidize and disperse in airflow, and the lower adhesion force between particles enabled drugs to be detached from the carrier to achieve higher fine particle fractions. The specific mechanism on how physicochemical properties influenced the aerosolization performance during the pulmonary delivery processes could be figured out with the introduction of powder properties.

Influence of surface interaction between drug and excipient in binary mixture for dry powder inhaler applications

The present study documents the drug-excipient incompatibility in the physical mixtures and its influence on bulk homogeneity and flowability for dry powder inhalers (DPI) applications. Binary mixtures with the model drugs (aceclofenac; salbutamol sulphate) and lactose monohydrate were prepared separately at varied drug loading (1–33 wt.%), and their physicochemical properties were assessed using various characterization techniques. The DSC, P-XRD and FT-IR studies show a significant shift in the signature peak of drug and excipient while ss-NMR, LC-MS show the absence of peaks. In contrast, new peaks are observed in LC-MS and GC studies. The insights are comprehended through a series of XPS studies. The findings indicated the formation of condensed or addition compound. This is attributed to an interaction between polar protic groups (-NH-, -COOH, -OH) and hemiacetal carbon (HO-C-OR) of drug and excipient in the solid-state. It induces crystal strain and alters bulk properties related to mixing (relative standard deviation, %RSD), cohesion and flow function coefficient (FFC). However, surface modification of excipient using MgSt and aerosil R972 (model nano-particle) eliminates such inter-particle interactions, crystal level changes. It improves the bulk properties of binary mixtures pivotal for DPI performance.

The Influence of Relative Humidity and Storage Conditions on the Physico-chemical Properties of Inhalation Grade Fine Lactose.

Dry powder inhalers (DPIs) are favorable devices for the delivery of dry formulations to the lungs; still, they largely fail to deliver higher doses of active pharmaceutical ingredient (API) to the lower airways. Addition of fine particles of excipient (fines) to the blend of API and carrier was shown to improve aerosolization performance. Lactose monohydrate is ubiquitous excipient used for this purpose. Lactose exists in a thermodynamically stable crystalline form; however, processes like milling, sieving, or even mixing may induce alteration of crystalline structure and introduce amorphous domains, which could further affect the physico-chemical properties of the material. Therefore, the aim of this work is a detailed characterization of two commercially available types of inhalation grade fine lactose powders (Inhalac 400 and Inhalac 500) prepared using different air-jet milling parameters, with a focus on impact of storage conditions on material properties. We found that the different milling parameters resulted in variable particle size distribution (PSD), and thus surface areas, variable initial amorphous content, cohesivity, flowability, and moisture sorption of materials. In addition, exposure of fine powders to higher humidity reduced the amorphous content present in the materials, but also affected agglomeration tendency and dispersion behavior of both powders. We believe the obtained findings to be important for the aerosolization performance of carrier-based DPIs containing fines and thus need to be duly considered during formulation development.

In Vitro Performance of the Wixela Inhub Inhaler Using Severe Chronic Obstructive Pulmonary Disease Patient Inhalation Profiles.

Background: Wixela Inhub (trademarks of Viatris, Inc.) is a dry powder inhaler (DPI) that delivers a fixed-dose combination of fluticasone propionate and salmeterol and is approved as a generic equivalent to Advair Diskus (trademarks of GlaxoSmithKline plc) for the treatment of asthma and chronic obstructive pulmonary disease (COPD). The dosing performance of DPIs is dependent on the patient's inspiratory capability, which may be impacted in disease populations such as those with severe COPD. The objective of this study was to evaluate the in vitro dose delivery of fluticasone propionate and salmeterol from the Inhub inhaler with in vivo inhalation profiles of severe COPD patients, using two types of breathing simulator with different modes of operation. Materials and Methods: Two breathing simulators (Si-Plan and Copley BRS3100) were used with United States Pharmacopoeia (USP) <601> apparatus 5 (Next Generation Impactor and accessories) to measure the total emitted dose and fine particle mass of fluticasone propionate and salmeterol for Wixela Inhub (250/50 mcg) using 13 severe COPD patient inhalation profiles. Results: Wixela Inhub demonstrated low flow dependency across the range of COPD patient profiles tested (peak inspiratory flow rate 60.8-84.9 L minute-1), when assessed by total emitted dose and fine particle mass. The results were similar to literature results reported for fluticasone propionate from the Diskus inhaler, tested using a proprietary breathing simulator and Andersen Cascade Impactor. Comparison between the breathing simulators showed no significant difference in fluticasone propionate results, but a small difference was observed between the breathing simulators for salmeterol total emitted dose and fine particle mass. Conclusions: This study demonstrates that severe COPD patients are likely to achieve a consistent inhaled dose from Wixela Inhub, with low flow dependency observed within this patient population. In addition, both breathing simulators, which differ significantly in design, produced similar results for fluticasone propionate, but yielded slightly (but statistically significant) different results for salmeterol.

A real-time and modular approach for quick detection and mechanism exploration of DPIs with different carrier particle sizes

Dry powder inhalers (DPIs) had been widely used in lung diseases on account of direct pulmonary delivery, good drug stability and satisfactory patient compliance. However, an indistinct understanding of pulmonary delivery processes (PDPs) hindered the development of DPIs. Most current evaluation methods explored the PDPs with over-simplified models, leading to uncompleted investigations of the whole or partial PDPs. In the present research, an innovative modular process analysis platform (MPAP) was applied to investigate the detailed mechanisms of each PDP of DPIs with different carrier particle sizes (CPS). The MPAP was composed of a laser particle size analyzer, an inhaler device, an artificial throat and a pre-separator, to investigate the fluidization and dispersion, transportation, detachment and deposition process of DPIs. The release profiles of drug, drug aggregation and carrier were monitored in real-time. The influence of CPS on PDPs and corresponding mechanisms were explored. The powder properties of the carriers were investigated by the optical profiler and Freeman Technology four powder rheometer. The next generation impactor was employed to explore the aerosolization performance of DPIs. The novel MPAP was successfully applied in exploring the comprehensive mechanism of PDPs, which had enormous potential to be used to investigate and develop DPIs.

Lattice–Boltzmann simulations for analysing the detachment of micron-sized spherical particles from surfaces with large-scale roughness structures

Fully resolved numerical simulations of a micron-sized spherical particle residing on a surface with large-scale roughness are performed by using the Lattice–Boltzmann method. The aim is to investigate the influence of surface roughness on the detachment of fine drug particles from larger carrier particles for transporting fine drug particles in a DPI (dry powder inhaler). Often the carrier surface is modified by mechanical treatments for modifying the surface roughness in order to reduce the adhesion force of drug particles. Therefore, drug particle removal from the carrier surface is equivalent to the detachment of a sphere from a rough plane surface. Here a sphere with a diameter of 5 μm at a particle Reynolds number of 1.0, 3.5 and 10 are considered. The surface roughness is described as regularly spaced semi-cylindrical asperities (with the axes oriented normal to the flow direction) on a smooth surface. The influence of asperity distance and size ratio (i.e. the radius of the semi-cylinder to the particle radius, Rc/Rd) on particle adhesion and detachment are studied. The asperity distance is varied in the range 1.2 <L/Rd < 2 and the semi-cylinder radius between 0.5 <Rc/Rd < 0.75. The required particle resolution and domain size are appropriately selected based on numerical studies, and a parametric analysis is performed to investigate the relationship between the contact distance (i.e. half the distance between the particle contact points on two neighbouring semi-cylinders), the asperity distance, the size ratio, and the height of the particle centroid from the plane wall. The drag, lift and torque acting on the spherical particle are measured for different particle Reynolds numbers, asperity distances and sizes or diameters. The detachment of particles from rough surfaces can occur through lift-off, sliding and rolling, and the corresponding detachment models are constructed for the case of rough surfaces. These studies will be the basis for developing Lagrangian detachment models that eventually should allow the optimisation of dry powder inhaler performance through computational fluid dynamics.

Inhalation Profiles Through a Dry Powder Inhaler: Relation Between Inhalation Technique and Spirometric Measures.

Background: The understanding of the real flow profiles through a dry powder inhaler (DPI), generated by asthma patients, is a prerequisite for satisfactory drug delivery to the lungs. The aims of the study were to assess the relationship between spirometric measures and inhalation profiles through a low-resistance DPI, and to compare parameters of those profiles between optimal and suboptimal inhalation technique type. Methods: Both healthy adult volunteers and patients with asthma were included in the study. Spirometry was conducted along with modified flow-volume test to detect expiratory levels (maximum "100%" exhalation to residual volume [RV] and halfway "50%" to RV). These were the reference levels of the depth of exhalation for each patient to simulate the effect of incomplete exhalation. Individual inhalation profiles were recorded using spirometry in-house software as the volumetric airflow through the inhaler versus time. Inspiratory flow parameters were extracted: time to peak inspiratory flow through inhaler (PIFinh), time at which peak inspiratory flow occurs (tPIFinh), total inhalation time (T), and inhaled volume during maneuver (V). Results and Conclusions: There are significant relationships between spirometric indices and parameters of inhalation through a low-resistance, cyclohaler-type DPI (assessed by single-factor analysis of Spearman's rank correlation coefficient). Multiple regression models were constructed, predicting inspiratory flow parameters (including spirometric indices, demographic parameters, and inhaler's usage history as determinants). The exhalation halfway to RV before inhalation did not affect significantly PIFinh and tPIFinh (and, thus, initial flow dynamics) in asthma patients. T and V parameters were then significantly decreased, but seemed sufficient for successful DPI performance. Both exhalation to RV and incomplete exhalation halfway to RV preceding inhalation allow for effective usage of low-resistance DPI.

Physicochemical analysis techniques specialized in surface characterization of inhalable dry powders

Dry powder inhaler (DPI) formulations are highly efficient in pulmonary drug delivery because devices for their delivery are portable and aerosolization does not require a propellant. The performance of DPIs depends on various physical properties of particles for their manufacture, including aerodynamic diameter, density, particle shape, surface composition, morphology, roughness, and energy. Among these, particle surface properties are the most important factors in determining the interparticulate interactions, which affect the aerosolization efficiency, physicochemical stability, and subsequent in vivo lung deposition efficiency. For a better understanding of the correlation between surface properties and the performance of DPI, there is the need to perform surface characterization of the DPI. This review focuses on analysis of the technology used in the design of DPIs. Thus, the surface crystallinity and polymorphism, surface energy, surface roughness, and changes in solid-state properties of the particles used in DPI formulation will be determined. The commonly used solid-state techniques may not be appropriate for the characterization of DPIs because their detection is mainly limited to the fine changes in physicochemical surface properties such as partial amorphous contents generated on the drug particle surface. Thus, sophisticated technologies with higher detection limits and superior spatial resolutions are required for in-depth characterization. Data obtained from surface analytical techniques can lead to an in-depth understanding of inhalable dry powder at the particle surface. This can provide unique predictive insights into rationally designing inhalable particles with optimal surface properties to provide optimal aerosolization performance for a given DPI formulation.

Understanding Carrier Performance in Low-Dose Dry Powder Inhalation: An In Vitro-In Silico Approach.

The use of physiologically based pharmacokinetic (PBPK) models to support drug product development has become increasingly popular. The in vitro characterization of the materials of the formulation provides valuable descriptors for the in silico prediction of the drug’s pharmacokinetic profile. Thus, the application of an in vitro–in silico framework can be decisive towards the prediction of the in vivo performance of a new medicine. By applying such an approach, this work aimed to derive mechanistic based insights into the potential impact of carrier particles and powder bulk properties on the in vivo performance of a lactose-based dry powder inhaler (DPI). For this, a PBPK model was developed using salbutamol sulphate (SS) as a model drug and the in vitro performance of its low-dose blends (2% w/w) with different types of lactose particles was investigated using different DPI types (capsule versus reservoir) at distinct airflows. Likewise, the influence of various carrier’s particle and bulk properties, device type and airflow were investigated in silico. Results showed that for the capsule-based device, low-dose blends of SS had a better performance, when smaller carrier particles (Dv0.5 ≈ 50 μm) with about 10% of fines were used. This resulted in a better predicted bioavailability of the drug for all the tested airflows. For the reservoir type DPI, the mean particle size (Dv0.5) was identified as the critical parameter impacting performance. Shear cell and air permeability or compressibility measurements, particle size distribution by pressure titration and the tensile strength of the selected lactose carrier powders were found useful to generate descriptors that could anticipate the potential in vivo performance of the tested DPI blends.

Dynamics of aerosol generation and release – Dry powder inhaler performance considerations

The main objective of the work was to investigate how the dynamics of inhalation affect aerosol release process in real-time, with an unsteady airflow through passive dry powder inhalers (DPIs) of comparable airflow resistance, but different principle of powder release. It consists of two complementary studies, concerning dynamics of controlled aerosol release (emission kinetics) and dynamics of aerosol generation (aerosol size characteristics in time series).Aerosol behavior of the powder was studied experimentally at the outlet of the inhalers: RS01 inhaler (Plastiape Spa, Osnago LC, Lombardy, Italy) and Turbospin (Ph&T, Milano, Lombardy, Italy). Two breathing profiles were analyzed throughout the study. Timing of aerosol emission was done by light scattering. Aerosol characterization was done by laser diffraction. It resulted in time evolution of volume concentration and volumetric particle size distribution.Both the design of the passive DPI inhaler and the dynamics of the inhalation (along with its intensification) influence the course of the aerosol generation and emission. The process of aerosol emission occurs only in the initial part of the inhalation process, before the peak inspiratory flow rate is established. This part is strongly responsible for the quality of the aerosol emitted from the device and consequently will potentially influence the drug delivery.

Effect of USP induction ports and modified glass sampling apparatus on aerosolization performance of lactose carrier-based fluticasone propionate dry powder inhaler

In the present study, a lactose based dry powder inhaler (DPI) was formulated to probe the effect of three different US Pharmacopeia (USP) induction port (IP) on aerosolization performance DPIs. Additionally, the delivered dose uniformity (DDU) and drug-carrier detachment were studied using the USP modified glass sampling apparatus and force-displacement concept, respectively. Initially, median sized lactose carrier (InhaLac® 160) and a model drug fluticasone propionate (FP) were studied for numerous physicochemical properties. The homogenous drug-carrier blend was prepared using a low shear 3D shaker mixer. The InhaLac® 160 showed typical tomahawk-shaped particles with mean particle size (d50) and average surface roughness of 109.46 μm and 2.70 μm, respectively. Additionally, the laser Raman spectrometry demonstrated the uniform surface distribution of FP across the carrier surface. In the drug-carrier detachment study, FP DPI required >600 g-force to detach the 50% of the FP particles from lactose surface. During cascade analysis, all three USP IPs showed a remarkable variation in drug retention within the IP and pre-separator. The USP modified IP showed superior % fine particle fraction as compared to the USP IP. The difference in aerodynamic dispersion can be attributed to the variation in the design of the USP IPs. Moreover, developed FP DPI showed satisfactory DDU (>88%) when studied using the modified glass sampling apparatus. Briefly, the present study offers a detailed report on aerosolization performance of median sized lactose carrier-based DPIs using different USP IPs.

Exploring the impact of extrinsic lactose fines, a USP modified sampling device and modified centrifuge tube on the delivered dose uniformity and drug detachment performance of a fluticasone propionate dry powder inhaler

The present study aimed to probe influences exerted by extrinsic lactose fines on drug detachment and delivered dose uniformity (DDU) of fluticasone propionate (FP) dry powder inhaler (DPI). Extrinsic lactose fines (0–35%) containing lactose pre-blends were formulated using a low shear 3D shaker mixer and systematically analyzed for various physicochemical properties. Moreover, formulated FP DPIs were assessed for drug detachment by force distribution concept and the DDU using two different sampling devices i.e. the Dosage Unit Sampling Apparatus (DUSA) and USP modified glass sampling device (modified DUSA) coupled with Aerolizer® device at 60 L/min. The physicochemical assessment of control and pre-blend lactose samples displayed significant differences in particle size, surface roughness, degree of surface irregularity and powder flow properties. The formulated FP DPIs displayed monolayer-type FP distribution across the lactose particles in laser Raman spectroscopy with acceptable content uniformity (~100%). Drug detachment study using a modified centrifuge tube showed significant differences in drug detachment profile. The FP DPI formulated using 20% of lactose fines showed the lowest drug detachment force (349.45 gf) as compared to the other lactose samples. Moreover, the FP DPI formulated using 20% of lactose fines demonstrated acceptable mean delivered dose (107.76 and 110.62 μg) with the lowest coefficient of variation using DUSA and modified DUSA, respectively. The present study is the first comprehensive summary of delivered dose uniformity using two different USP sampling devices. Accordingly, these observations may be of high significance for both intuitional and industrial formulators.

Co-spraying of carriers (mannitol-lactose) as a method to improve aerosolization performance of salbutamol sulfate dry powder inhaler

Although in dry powder inhaler (DPI) formulations a single carrier is used, a single carrier is not able to provide an excellent aerosolization performance when it is used in DPI formulations. Thereby, the aim of this study was to engineer a suitable ternary mixture of mannitol-lactose-leucine to be used in a DPI formulation with enhanced aerosolization performance. To this end, binary mixtures of mannitol:lactose containing a constant amount of leucine (5% w/w of carriers) were spray-dried as a single solution. Spray-dried samples were blended with salbutamol sulfate to determine the efficiency of their aerosolization performance. Interestingly, note that lactose was in its amorphous state stabilized by the presence of mannitol in the samples. Spray-dried mannitol without lactose showed a combination of the α- and β-polymorphic forms which was the case in all other ratios of mannitol:lactose. It was shown that the highest fine particle fraction (FPF) was 62.42 ± 4.21% which was obtained for the distinct binary mixtures (1:3 mannitol:lactose) compared to a single carrier. This study opens a new window to investigate further the implementation of binary mixtures of sugar carriers containing leucine in DPI formulations to overcome poor aerosolization performance the mentioned DPI formulations.

Investigation of Electrostatic Behavior of Dry Powder-Inhaled Model Formulations

The accumulation of electrostatic charge on drug particles and excipient powders arising from interparticulate collisions or contacts with other surfaces can lead to agglomeration and adhesion problems during the manufacturing process, filling, and delivery of dry powder inhaler (DPI) formulations. The objective of the study was to investigate the role of triboelectrification to better understand the influence of electrostatic charge on the performance of DPIs with 2 capsule-based dimensionally similar devices constructed with different materials. In addition, strategies to reduce electrostatic charge build up during the manufacturing process, and the processes involved in this phenomenon were investigated. Electrostatic charge measurements showed that there was a significant difference in electrostatic charge generated between tested formulations and devices. This affects particle detachment from carrier and thus significantly impacts aerosol performance. Conditioning fluticasone DPI capsules at defined temperature and humidity conditions reduced electrostatic charges acquired during manufacturing. Conditioning salmeterol DPI capsules at same conditions seemed disadvantageous for their aerosol performance because of increasing capillary forces and solid bridge formation caused by water absorption. Knowledge and understanding of the role of electrostatic forces in influencing DPI formulation performance was increased by these studies.