Commercial Dry Powder Inhaler Research Articles

Compatibility study of formoterol fumarate-lactose dry powder inhalation formulations: Spray drying, physical mixture and commercial DPIs

Formoterol fumarate (FF) is a long-acting beta-adrenergic receptor agonist that is administered as a dry powder inhaler (DPI) for chronic respiratory conditions. In most DPI formulations, the drug substance and the carrier are the two major components. Lactose is the most common carrier, which can undergo a Maillard reaction in the presence of primary and secondary amines. FF contains a secondary amine. Since the potential for Maillard reaction in DPI formulations has not been investigated yet, this study aims to investigate any potential reaction between lactose and FF. The formulations were prepared using a tubular mixer and spray drying techniques. FF and lactose were blended using a tubular mixer (TM FF-Lac). In the spray drying method, FF and lactose were dissolved in distilled water: MeOH and then spray dried (SD FF-Lac). The samples were stored at both ambient conditions and elevated temperature and humidity (40 °C ± 2, 75% ± 5 RH), and subsequently analyzed to identify any signs of incompatibilities. Differential scanning calorimetry (DSC), field emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), and liquid chromatography-mass spectrometry (LC-MS-MS) were employed for sample analysis. The in vitro aerosolization performance was evaluated using a next-generation impactor (NGI). The results showed that the colour of the DPI formulations changed from white to brown after storage at elevated temperature and humidity. Although the SD FF-Lac had better aerosolization properties, it was more vulnerable to degradation due to its amorphous nature. The FF-lactose adduct was formed in all samples. Interestingly, adduct compounds were also detectable before the storage for stability and stress tests. Incompatibility was confirmed by HPLC-PDA analysis. The mass spectra revealed the m/z of the adduct compound and confirmed the Millard reaction. Browning occurred in the prepared DPI formulations following storage at elevated temperature and humidity. Moreover, adduct compounds were also found in DPI formulations kept at ambient conditions and commercial DPI. Overall, mass spectroscopy was capable of detecting the incompatibility.

CFD-DEM investigation of the dispersion of elongated particles in the Turbuhaler® aerosol device

Elongated drug particles have the potential to be superior to spherical drug particles for delivery to the deep lung due to their increased ability to align with the airflow. However, the performance of elongated particles within dry powder inhalers (DPIs) has been largely unexplored. This paper presented a CFD-DEM study to simulate the dispersion of elongated active pharmaceutical ingredient (API) particles with equivalent sizes of 1.55–5.53 μm in a commercial DPI device Turbuhaler®. The model, which adopted a multi-sphere approach to mimic the shape of elongated spherocylindrical particles, was validated by comparing experimental data of fluidized beds. The model was then utilized to simulate the dispersion of powders with different aspect ratios in Turbuhaler. Findings revealed that the depositions of elongated particles in the chamber and the mouthpiece were significantly higher than those of spherical particles, and the depositions increased with higher aspect ratios. The higher deposition of the elongated particles was due to much stronger inter-particle cohesion when particles were in flat contact with particles or wall surfaces. Similar to spherical particles, both emitted dose and fine particle fraction (FPF, % mass of particles below 5 μm) of elongated particles increased with flow rates due to intensified particle-wall collisions. On the other hand, the FPF of elongated particles in the device decreased more significantly with increasing cohesion than spherical particles. Results indicated that while elongated particles are preferred for drug delivery to deeper lungs, their poor dispersion in inhalers due to higher deposition needs to be considered.

Effects of the mouthpiece and chamber of Turbuhaler® on the aerosolization of API-only powder formulations

Powder dispersion in dry powder inhalers (DPIs) is affected by powder formulations as well as the design of a device. This paper conducted a numerical investigation based on the coupled computational fluid dynamics (CFD) and discrete element method (DEM) to evaluate the changes of the design of a commercial DPI device Turbuhaler® on the aerosolization of an API-only formulation. Six different designs were proposed by modifying the mouthpiece and chamber of the original geometry which was reconstructed from a CT-scan of the Turbuhaler, and their performances in terms of powder deposition in the device and fine powder fraction (FPF) were evaluated. The resistance of the device was observed to vary with different designs. For the change of the mouthpiece, the device with a cylindrical mouthpiece had the least resistance and the lowest FPF emitted among all the devices, confirming the important role of the spiral mouthpiece on powder dispersion. Reducing the mouthpiece size caused more powder deposition in the inhaler due to higher airflow velocity, but FPF emitted increased compared to the original design as more powder dispersion occurred inside the mouthpiece. The half-length mouthpiece design reduced device resistance to increase airflow velocity and average collision energy, resulting in an increase in FPF loaded but a decrease in the number of collisions. For the change of the chamber, the domed chamber design increased the powder dispersion time and thus enhanced the frequency and energy of particle collisions, which eventually led to an increase in FPF loaded. At fixed flow rates, the powder dispersion efficiency was a function of the device resistance with higher device resistance causing an increase in the FPF loaded. However, it is important for the patient’s attainable pressure drop to be considered in this context. Correlations between the aerosolization efficiency and the ratio of the average collision energy and cohesion energy were established based on model-predicted quantities.

Lack of CB1 receptor reduces preterm birth rate in an LPS-induced murine model

Dry powder inhalers (DPIs) are known to be sensitive to humidity. Erroneous storage of these products by patients in high humidity environments, could present a potential risk. Therefore, an in-vitro-in-silico approach was utilized to assess the risk that patient erroneous storage might pose. For this two commercial DPIs containing lactose and budesonide (Easyhaler® and Novolizer®) were used. These were evaluated in respect to their physical solid-state and micrometric properties as well as their in-vitro aerodynamic performance. Testing was carried out at time 0, 14 and 28 days after storage at 60% RH and > 90% RH. Using in-silico modeling the potential impact of powder sensitivity to humidity on the biopharmaceutical performance of budesonide was evaluated. Results revealed that the physical and aerodynamic properties of the powders having a smaller carrier particle size and a higher amount of excipient fines were more notably affected. Use of in-vitro results as inputs for in-silico pharmacokinetic modeling showed that some changes in powder properties can have a potential impact on the pulmonary availability of budesonide. So, it appears that it is important to consider the impact that different product characteristics might have on the physical stability of powders against moisture and their subsequent biopharmaceutical performance.

From laminar to turbulent flow in a dry powder inhaler: The effect of simple design modifications

In order to better understand powder dispersion in dry powder inhaler (DPI) devices, a new powder disperser was designed, which uses flow modifiers to alter powder fluidization behavior so as to physically replicate various flow conditions observed in a range of commercial DPIs. The influence of these modifiers on the performance of the DPI was analyzed for flowrates progressing from laminar (15 L/min) to transitional (30 L/min), and finally turbulent flow regimes (60 L/min) in the device. The aerosol performance of the disperser was measured using a Next Generation Impactor. For flowrate in the laminar regime, powder evacuation from the disperser was generally insufficient (<30%), which was increased to >85% when the device was operated in the turbulent flow regime. In contrast, the highest fine particle fraction (FPF) and lowest throat deposition were achieved when operating in the transitional flow regime. The FPF could be increased further by applying flow modifications such as narrowing the air passage before the powder pocket, inducing localized turbulence (by a grid) near the powder pocket, and by changing the loading position of the powder. Flow modifiers had the most noticeable effect under a laminar flow regime, however, the device operated most efficiently under a transitional flow regime.

Optimization of swirler type dry powder inhaler device design – Numerical investigation on the effect of dimple shape, inlet configuration and mouthpiece constriction

Dry powder inhalers (DPIs) are recognized as one of the most convenient drug delivery devices via the respiratory tract. However, there is a large variation in their dispersion efficiencies due to the cohesive nature of the inhalable pharmaceutical powders. This paper presents a thorough numerical investigation of the effect of various design modifications in swirler type DPI devices. One-way coupled Computational Fluid Dynamics-Discrete Phase Modeling simulations were implemented to evaluate the flow field and particle behaviour in DPIs under 60 L/min inhalation condition. The dispersion behaviour of entrained particles in relation to the particle-wall impactions was evaluated in six different in-house designed and one commercial DPI devices, with variations in dimple shape, inlet orientation, inlet numbers, and mouthpiece pipe constriction. We found that the shape of dimples varies the swirling capability of both fluid and particles and mouthpiece pipe constriction reduced the turbulence kinetic energy. Meanwhile, the axial velocity and impaction frequency are increased as the size of particles are increased. The constriction of mouthpiece pipe did not show significant improvement on the frequency of particle-wall impactions for particles smaller than 10 μm, whilst higher impaction frequencies were observed for particles larger than 10 μm. Overall, the sphere shape dimples with mouthpiece pipe constricted design is optimal in terms of device efficiency.

Evaluation of the stability of a spray-dried tuberculosis vaccine candidate designed for dry powder respiratory delivery

Particle engineering via spray drying was used to develop a dry powder presentation of an adjuvanted tuberculosis vaccine candidate. This presentation utilizing a trileucine-trehalose excipient system was designed to be both thermostable and suitable for respiratory delivery. The stability of the spray-dried vaccine powder was assessed over one year at various storage temperatures (-20, 5, 25, 40, 50 °C) in terms of powder stability, adjuvant stability, and antigen stability. A formulation without trileucine was included as a control. The results showed that the interior particle structure and exterior particle morphology of the powder was maintained for one year at 40 °C, while the control case exhibited a small extent of particle fusing under the same storage conditions. Moisture content was maintained, and powder solid state remained amorphous for all storage temperatures. Aerosol performance was assessed with a commercial dry powder inhaler in combination with a human mouth-throat model. The emitted dose and lung dose were maintained for all samples after one year at temperatures up to 40 °C. Nanoemulsion size and oil content of the adjuvant system were maintained after one year at temperatures up to 40 °C, and the agonist content was maintained after one year at temperatures up to 25 °C. The antigen was completely degraded in the control formulation at seven months of storage at 40 °C; by contrast, 45% of the antigen was still present in the trehalose-trileucine formulation after one year of storage at 50 °C. Comparatively, the antigen was completely degraded in a liquid sample of the vaccine candidate after only one month of storage at 37 °C. The spray-dried trehalose-trileucine vaccine powder clearly maintained its inhalable properties after one year’s storage at high temperatures and improved overall thermostability of the vaccine.

Administration of dry powders during respiratory supports.

Inhaled drugs are routinely used for the treatment of respiratory-supported patients. To date, pressurized metered dose inhalers and nebulizers are the two platforms routinely employed in the clinical setting. The scarce utilization of the dry powder inhaler (DPI) platform is partly due to the lack of in vivo data that proves optimal delivery and drug efficacy are achievable. Additionally, fitting a DPI in-line to the respiratory circuit is not as straightforward as with the other aerosol delivery platforms. Importantly, there is a common misconception that the warm and humidified inspiratory air in respiratory supports, even for a short exposure, will deteriorate powder formulation compromising its delivery and efficacy. However, some recent studies have dispelled this myth, showing successful delivery of dry powders through the humidified circuit of respiratory supports. Compared with other aerosol delivery devices, the use of DPIs during respiratory supports possesses unique advantages such as rapid delivery and high dose. In this review, we presented in vitro studies showing various setups employing commercial DPIs and effects of ventilator parameters on the aerosol delivery. Inclusion of novel DPIs was also made to illustrate characteristics of an ideal inhaler that would give high lung dose with low powder deposition loss in tracheal tubes and respiratory circuits. Clinical trials are urgently needed to confirm the benefits of administration of dry powders in ventilated patients, thus enabling translation of powder delivery into practice.

Insights into DPI sensitivity to humidity: An integrated in-vitro-in-silico risk-assessment

Dry powder inhalers (DPIs) are known to be sensitive to humidity. Erroneous storage of these products by patients in high humidity environments, could present a potential risk. Therefore, an in-vitro-in-silico approach was utilized to assess the risk that patient erroneous storage might pose. For this two commercial DPIs containing lactose and budesonide (Easyhaler® and Novolizer®) were used. These were evaluated in respect to their physical solid-state and micrometric properties as well as their in-vitro aerodynamic performance. Testing was carried out at time 0, 14 and 28 days after storage at 60% RH and > 90% RH. Using in-silico modeling the potential impact of powder sensitivity to humidity on the biopharmaceutical performance of budesonide was evaluated. Results revealed that the physical and aerodynamic properties of the powders having a smaller carrier particle size and a higher amount of excipient fines were more notably affected. Use of in-vitro results as inputs for in-silico pharmacokinetic modeling showed that some changes in powder properties can have a potential impact on the pulmonary availability of budesonide. So, it appears that it is important to consider the impact that different product characteristics might have on the physical stability of powders against moisture and their subsequent biopharmaceutical performance.

Amorphous pullulan trehalose microparticle platform for respiratory delivery

Spray drying biologics and small-molecule drugs can increase their thermal stability relative to liquid dosage forms and allow for widespread distribution to developing countries without cold chain infrastructure. In this study, pullulan trehalose powder is spray dried for inhalation. The powder is characterized in terms of manufacturability, physical stability, device compatibility, and aerosol performance. The manufacturability is demonstrated by reasonable spray drying yield and powder flowability. The powder has relatively low cohesiveness and high compressibility without semi-elastic deformation. Short-term physical stability for ambient temperature dry storage and 40 °C storage in commercial pressurized metered-dose inhaler propellants HFA 134a and HFA 227 is shown. A theoretical model predicts a high glass transition temperature near the surface of the microparticles where biologics are expected to reside. Emission from a commercial dry powder inhaler demonstrates high dispersibility, optimal size for inhalation, and adequate total lung dose, exceeding many commercial inhalation devices. The powder can be filled, stored, and actuated from a pressurized metered-dose inhaler without changes in particle morphology or solid phase. The pullulan trehalose platform thus appears promising for respiratory delivery.

Critical physicochemical attributes of chitosan nanoparticles admixed lactose-PEG 3000 microparticles in pulmonary inhalation

Chitosan nanoparticles are exhalation prone and agglomerative to pulmonary inhalation. Blending nanoparticles with lactose microparticles (∼5 µm) could mutually reduce their agglomeration through surface adsorption phenomenon. The chitosan nanoparticles of varying size, size distribution, zeta potential, crystallinity, shape and surface roughness were prepared by spray drying technique as a function of chitosan, surfactant and processing conditions. Lactose-polyethylene glycol 3000 (PEG3000) microparticles were similarly prepared. The chitosan nanoparticles, physically blended with fine lactose-PEG3000 microparticles, exhibited a comparable inhalation performance with the commercial dry powder inhaler products (fine particle fraction between 20% and 30%). Cascade impactor analysis indicated that the aerosolization and inhalation performance of chitosan nanoparticles was promoted by their higher zeta potential and circularity, and larger size attributes of which led to reduced inter-nanoparticulate aggregation and favored nanoparticles interacting with lactose-PEG3000 micropaticles that aided their delivery into deep and peripheral lungs.

InVitro Evaluation of Optimal Inhalation Flow Patterns for Commercial Dry Powder Inhalers and Pressurized Metered Dose Inhalers With Human Inhalation Flow Pattern Simulator

This study aimed at developing a novel analytical method to identify optimal inhalation flow patterns for commercial dry powder inhalers (DPIs) and pressurized metered dose inhalers (pMDIs). As typical commercial DPI and pMDI, Pulmicort® Turbuhaler®, and Sultanol® Inhaler were evaluated by an in vitro inhalation performance testing system with a flow pattern simulator. An 8-stage Andersen cascade impactor (ACI) or twin stage liquid impinger (TSLI) was applied to determine the inhalation performance. The peak flow rate (PFR) of the inhalation flow pattern was set from 15 to 80 L/min in reference to our previous study. From TSLI test results, a higher PFR improved the inhalation performance of the DPI, while the performance of the pMDI was less affected by the PFR. Conversely, from ACI test results, the pMDI performance decreased with a higher PFR, while the DPI followed a similar pattern as in the TSLI test results, because ACI is a finer aerodynamic classification apparatus than TSLI. These results suggested that our in vitro system using a human inhalation flow pattern simulator successfully detected different optimal inhalation patterns between DPI and pMDI. That is, the higher PFR is better for Pulmicort® Turbuhaler® (DPI). Conversely, lower PFR is desirable for Sultanol® Inhaler (pMDI).

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.

Optimization of a DPI Inhaler: A Computational Approach

Alternate geometries of a commercial dry powder inhaler (DPI, i.e., Turbuhaler; AstraZeneca, London, UK) are proposed based on the simulation results obtained from a fluid and particle dynamic computational model, previously developed by Milenkovic et al. The alternate DPI geometries are constructed by simple alterations to components of the commercial inhaler device leading to smoother flow patterns in regions where significant particle-wall collisions occur. The modified DPIs are investigated under the same conditions of the original studies of Milenkovic et al. for a wide range of inhalation flow rates (i.e., 30-70 L/min). Based on the computational results in terms of total particle deposition and fine particle fraction, the modified DPIs were improved over the original design of the commercial device.

Computationally efficient analysis of particle transport and deposition in a human whole-lung-airway model. Part II: Dry powder inhaler application

Pulmonary drug delivery is becoming a favored route for administering drugs to treat both lung and systemic diseases. Examples of lung diseases include asthma, cystic fibrosis and chronic obstructive pulmonary disease (COPD) as well as respiratory distress syndrome (ARDS) and pulmonary fibrosis. Special respiratory drugs are administered to the lungs, using an appropriate inhaler device. Next to the pressurized metered-dose inhaler (pMDI), the dry powder inhaler (DPI) is a frequently used device because of the good drug stability and a minimal need for patient coordination. Specific DPI-designs and operations greatly affect drug-aerosol formation and hence local lung deposition. Simulating the fluid-particle dynamics after use of a DPI allows for the assessment of drug-aerosol deposition and can also assist in improving the device configuration and operation. In Part I of this study a first-generation whole lung-airway model (WLAM) was introduced and discussed to analyze particle transport and deposition in a human respiratory tract model. In the present Part II the drug-aerosols are assumed to be injected into the lung airways from a DPI mouth-piece, forming the mouth-inlet. The total as well as regional particle depositions in the WLAM, as inhaled from a DPI, were successfully compared with experimental data sets reported in the open literature. The validated modeling methodology was then employed to study the delivery of curcumin aerosols into lung airways using a commercial DPI. Curcumin has been implicated to possess high therapeutic potential as an antioxidant, anti-inflammatory and anti-cancer agent. However, efficacy of curcumin treatment is limited because of the low bioavailability of curcumin when ingested. Hence, alternative drug administration techniques, e.g., using inhalable curcumin-aerosols, are under investigation. Based on the present results, it can be concluded that use of a DPI leads to low lung deposition efficiencies because large amounts of drugs are deposited in the oral cavity. Hence, the output of a modified DPI has been evaluated to achieve improved drug delivery, especially needed when targeting the smaller lung airways. This study is the first to utilize CF-PD methodology to simulate drug-aerosol transport and deposition under actual breathing conditions in a whole lung model, using a commercial dry-powder inhaler for realistic inlet conditions.

Computationally efficient analysis of particle transport and deposition in a human whole-lung-airway model. Part I: Theory and model validation

Computational predictions of aerosol transport and deposition in the human respiratory tract can assist in evaluating detrimental or therapeutic health effects when inhaling toxic particles or administering drugs. However, the sheer complexity of the human lung, featuring a total of 16 million tubular airways, prohibits detailed computer simulations of the fluid-particle dynamics for the entire respiratory system. Thus, in order to obtain useful and efficient particle deposition results, an alternative modeling approach is necessary where the whole-lung geometry is approximated and physiological boundary conditions are implemented to simulate breathing. In Part I, the present new whole-lung-airway model (WLAM) represents the actual lung geometry via a basic 3-D mouth-to-trachea configuration while all subsequent airways are lumped together, i.e., reduced to an exponentially expanding 1-D conduit. The diameter for each generation of the 1-D extension can be obtained on a subject-specific basis from the calculated total volume which represents each generation of the individual. The alveolar volume was added based on the approximate number of alveoli per generation. A wall-displacement boundary condition was applied at the bottom surface of the first-generation WLAM, so that any breathing pattern due to the negative alveolar pressure can be reproduced. Specifically, different inhalation/exhalation scenarios (rest, exercise, etc.) were implemented by controlling the wall/mesh displacements to simulate realistic breathing cycles in the WLAM. Total and regional particle deposition results agree with experimental lung deposition results. The outcomes provide critical insight to and quantitative results of aerosol deposition in human whole-lung airways with modest computational resources. Hence, the WLAM can be used in analyzing human exposure to toxic particulate matter or it can assist in estimating pharmacological effects of administered drug-aerosols. As a practical WLAM application, the transport and deposition of asthma drugs from a commercial dry-powder inhaler is discussed in Part II.

Abstracts from The Aerosol Society Drug Delivery to the Lungs 26 Edinburgh International Conference Centre Edinburgh, Scotland, UK December 9-11, 2015.

Abstracts from The Aerosol Society Drug Delivery to the Lungs 26 Edinburgh International Conference Centre Edinburgh, Scotland, UK December 9-11, 2015.

Improved lung delivery of budesonide from biopolymer based dry powder inhaler through natural inhalation of rat

Budesonide, an inhaled glucocorticoid, is used for the treatment of large and small calibre airway inflammation associated with asthma. Conventional dry powder inhalers (DPIs) show least deposition efficiency in the lung due to agglomeration, increased particle size and minimum fluidisation. There is a need for controlled release budesonide DPI in order to improve maximum lung deposition with least toxicity and improve patient compliance. Budesonide loaded biopolymer based microparticles were prepared by controlled gelation of sodium alginate using calcium chloride and chitosan. Microparticles were evaluated for physical characteristics, in vitro lung deposition by Andersen cascade impactor and in vivo regional lung deposition by fabricated apparatus with measured respiratory minute volume of rats from plethysmography. The effect of DPI on the histology of lung tissues was also studied. The particle size, encapsulation efficiency, ζ potential, mass median aerodynamic diameter and fine particle fraction of the DPI were 3·059±0·03 μm, 87·16±1·11%, −17·5 mV, 1·16±0·01 μm and 56·18±0·01% respectively, which revealed the potential for pulmonary delivery. Formulation demonstrated a 14-fold increased drug deposition in the lung as compared to commercial DPI indicating pulmonary targeting potential. The formulation showed the controlled drug release up to 24 h. The histopathology revealed safety of the formulation. Developed DPI markedly improved regional lung deposition and safety of budesonide. This technology would facilitate the administration of glucocorticoid in the clinical testing.

Deposition and fine particle production during dynamic flow in a dry powder inhaler: A CFD approach

In this work the dynamic flow as well as the particle motion and deposition in a commercial dry powder inhaler, DPI (i.e., Turbuhaler) is described using computational fluid dynamics, CFD. The dynamic flow model presented here is an extension of a steady flow model previously described in Milenkovic et al. (2013). The model integrates CFD simulations for dynamic flow, an Eulerian-fluid/Lagrangian-particle description of particle motion as well as a particle/wall interaction model providing the sticking efficiency of particles colliding with the DPI walls. The dynamic flow is imposed by a time varying outlet pressure and the particle injections into the DPI are assumed to occur instantaneously and follow a prescribed particle size distribution, PSD. The total particle deposition and the production of fine particles in the DPI are determined for different peak inspiratory flow rates, PIFR, flow increase rates, FIR, and particle injection times. The simulation results for particle deposition are found to agree well with available experimental data for different values of PIFR and FIR. The predicted values of fine particle fraction are in agreement with available experimental results when the mean size of the injected PSD is taken to depend on the PIFR.

The development of a sensitive methodology to characterise hard shell capsule puncture by dry powder inhaler pins

In order for hard-shell capsules to function effectively as drug reservoirs in dry powder inhalers, the capsule must be punctured with sharpened pins to release the powdered medicament upon inspiration. Capsule performance in this setting is poorly understood. This study aims to develop a methodology to characterise hard shell capsule penetration by needles from commercial dry powder inhalers, to determine whether changes to capsule materials impact on their performance. Two pin types from two commercial dry powder inhalers were mounted in a material-testing machine, equipped with a 500 N load cell. A stainless steel bush was used to secure a capsule directly below the steel pin. Hypromellose (n=10) and gelatin capsules (n=10) were conditioned in 'normal' or low humidity conditions and were subsequently punctured with both types of pin. Each puncture event was recorded on a load-displacement curve. The force required for puncture was 2.82±0.26 N for hypromellose capsules and 4.54±0.26 N for gelatin capsules, stored in normal humidity. Different capsule materials possessed distinguishable signature profiles but repeated force-displacement profiles were highly reproducible i.e. intra-individual variability was minimal. A rapid, robust yet sensitive methodology has therefore been developed that is able to characterise hard shell capsule materials based on the puncture performance.