Emitted Dose Research Articles

In-Vitro Characterization of the Aerosolized Dose During Non-Invasive Automatic Continuous Positive Airway Pressure Ventilation

Many devices (e.g., nebulizers and spacers) are used to deliver aerosol in a non-invasive ventilation circuit (NIV) without any special recommendation. The aim of the present work was to compare the doses delivered from seven different aerosol delivery systems when placed in the NIV using automatic continuous positive airway pressure (Auto-CPAP). Three spacers and three vibrating mesh nebulizers were compared to a Sidestream jet nebulizer (SIDE). Each device was placed proximal to a breathing simulator in a standard NIV circuit with a 500 ml tidal volume, 15 breaths/min and a 1:3 inspiratory-expiratory ratio. Two ml of salbutamol solution containing 10,000 μg was nebulized using Aerogen Pro (PRO), Aerogen Solo (SOLO), NIVO and SIDE. Twelve metered dose inhaler doses, containing 100 μg salbutamol each, were delivered using AeroChamber MV (AC), AeroChamber Vent (VC) and AeroChamber Mini (MC). Total emitted dose (TED) and its percentage were determined. Aerodynamic droplet characteristics were measured using cooled Andersen Cascade Impactor. The vibrating mesh nebulizers used had significantly more (p < 0.001) TED compared to the jet nebulizer. The spacers used had higher TED % (p < 0.001) compared to the nebulizers. The fine particle fraction of SIDE was the highest (p = 0.021) and mass median aerodynamic diameter of the spacers was the smallest (p = 0.001). The fine particle dose from vibrating mesh nebulizers was the greatest (p = 0.02). Aerosol delivery in Auto-CPAP NIV is feasible; however, aerosol delivery method should be chosen or substituted with care. 2 mg delivered from a spacer would be equivalent to 3 mg nebulized from a vibrating mesh nebulizer and 5 mg nebulized from a Sidestream.

In vitro/in vivo correlation and modeling of emitted dose and lung deposition of inhaled salbutamol from metered dose inhalers with different types of spacers in noninvasively ventilated patients

Substituting spacer by another in noninvasive ventilation (NIV) involves many variables, e.g. total emitted dose (TED), mass median aerodynamic diameter (MMAD), type of spacer, total lung deposition and total systemic absorption, which must be adjusted to ensure patient optimum therapy. Data mining based on artificial neural networks and genetic algorithms were used to model in vitro inhalation process, predict and optimize bioavailability from inhaled doses delivered by metered dose inhaler (MDI) using different spacers in NIV. Modeling of data indicated that in vitro performance of MDI-spacer systems was dependent mainly on fine particle dose (FPD), fine particle fraction (FPF), MMAD and to lesser extent on spacer type. Ex vivo model indicated that amount of salbutamol collected on facemask filter was directly affected by FPF. In vivo model (24hQ) depended directly on spacer type, FPF and TED. Female patients showed higher 0.5hQ and 24hQ values than males. AeroChamber VC spacer demonstrated higher TED and 24hQ in vivo values. Results indicated suitability of MDI-spacer systems in achieving appropriate in vitro inhalation performance. The possibility of modeling and predicting both ex vivo and in vivo capabilities of MDI-spacer systems from knowledge of in vitro attributes enabled detailed focus on important variables required to deliver safe and accurate doses of salbutamol to ventilated patients.

Effects of Surface Composition on the Aerosolisation and Dissolution of Inhaled Antibiotic Combination Powders Consisting of Colistin and Rifampicin.

Colistin is often the only effective antibiotic against the respiratory infections caused by multidrug-resistant Gram-negative bacteria. However, colistin-resistant multidrug-resistant isolates have been increasingly reported and combination therapy is preferred to combat resistance. In this study, five combination formulations containing colistin (COL) and rifampicin (RIF) were prepared by spray drying. The lowest minimum inhibitory concentration (MIC) value against Pseudomonas aeruginosa PAO1 was measured for the formulation of COL/RIF = 4:1 with relatively high emitted doses (over 80%) and satisfactory fine particle fractions (over 60%). Data from X-ray photoelectron spectroscopy (XPS) and nano-time-of-flight secondary ion mass spectrometry (ToF-SIMS) showed the surfaces of particles were mainly covered by rifampicin even for the formulation with a mass ratio of COL/RIF = 4:1. Because colistin is hygroscopic and rifampicin is hydrophobic, moisture absorption of combination formulations was significantly lower than the pure colistin formulation in the dynamic vapour sorption results. To investigate the dissolution characteristics, four dissolution test methods (diffusion Franz cell, modified Franz cell, flow-through and beaker methods) were employed and compared. The modified Franz cell method was selected to test the dissolution behaviour of aerosolised powder formulations to eliminate the effect of membrane on dissolution. The results showed that surface enrichment of hydrophobic rifampicin neither affected aerosolisation nor retarded dissolution rate of colistin in the combination formulations. For the first time, advanced surface characterisation techniques of XPS and ToF-SIMS have shown their capability to understand the effect of surface composition on the aerosolisation and dissolution of combination powders.

Comparing Radiation Dose from Conventional Fluoroscopy to Intraoperative Cone Beam CT (O-arm) during Percutaneous Lesioning Procedures of the Gasserian Ganglion.

Introduction: The use of intraoperative CT-guidance during the percutaneous treatment of trigeminal neuralgia has become increasingly popular due to the greater ease of foramen ovale cannulation and decreased procedure times. Concerns regarding radiation dose to the patient, however, remain unaddressed. We sought to compare the emitted radiation dose from fluoroscopy with intraoperative CT for these procedures.Methods: A retrospective review of percutaneous lesioning procedures for trigeminal neuralgia performed between 2010 until 2012 at our institution was conducted and radiation doses to the patient were recorded. We subsequently simulated four separate percutaneous trigeminal rhizotomies using the O-arm intraoperative CT (Medtronics, Minneapolis, MN, USA) to cannulate the foramen ovale bilaterally in two formalin-fixed cadaver heads.Results: Seventeen successful percutaneous treatments for trigeminal neuralgia were performed during the study period. Eleven procedures containing complete records were included in the final analysis. For procedures using fluoroscopy, the mean dosage was 15.2 mGys (range: 1.15 - 47.95, 95% CI 7.34 – 22.99). Radiation dosage from the O-arm imaging system was 16.55 mGy for all four cases. An unequal variance t-test did not reach statistical significance (p=0.42).Conclusions: We did not observe a significant difference in radiation dose delivered to subjects when comparing CT-guided foramen ovale cannulation relative to fluoroscopy for percutaneous lesioning of the Gasserian ganglion. Additional study is required under operational settings.

Preparation, optimization, and in vitro simulated inhalation delivery of carvedilol nanoparticles loaded on a coarse carrier intended for pulmonary administration.

Carvedilol (CAR) is a potent antihypertensive drug but has poor oral bioavailability (24%). A nanosuspension suitable for pulmonary delivery to enhance bioavailability and bypass first-pass metabolism of CAR could be advantageous. Accordingly, the aim of this work was to prepare CAR nanosuspensions and to use artificial neural networks associated with genetic algorithm to model and optimize the formulations. The optimized nanosuspension was lyophilized to obtain dry powder suitable for inhalation. However, respirable particles must have a diameter of 1–5 µm in order to deposit in the lungs. Hence, mannitol was used during lyophilization for cryoprotection and to act as a coarse carrier for nanoparticles in order to deliver them into their desired destination. The bottom-up technique was adopted for nanosuspension formulation using Pluronic stabilizers (F127, F68, and P123) combined with sodium deoxycholate at 1:1 weight ratio, at three levels with two drug loads and two aqueous to organic phase volume ratios. The drug crystallinity was studied using differential scanning calorimetry and powder X-ray diffractometry. The in vitro emitted doses of CAR were evaluated using a dry powder inhaler sampling apparatus and the aerodynamic characteristics were evaluated using an Andersen MKII cascade impactor. The artificial neural networks results showed that Pluronic F127 was the optimum stabilizer based on the desired particle size, polydispersity index, and zeta potential. Results of differential scanning calorimetry combined with powder X-ray diffractometry showed that CAR crystallinity was observed in the lyophilized nanosuspension. The aerodynamic characteristics of the optimized lyophilized nanosuspension demonstrated significantly higher percentage of total emitted dose (89.70%) and smaller mass median aerodynamic diameter (2.80 µm) compared with coarse drug powder (73.60% and 4.20 µm, respectively). In summary, the above strategy confirmed the applicability of formulating CAR in the form of nanoparticles loaded on a coarse carrier suitable for inhalation delivery.

Low altitude unmanned aerial vehicle for characterising remediation effectiveness following the FDNPP accident

On the 12th of March 2011, The Great Tōhoku Earthquake occurred 70 km off the eastern coast of Japan, generating a large 14 m high tsunami. The ensuing catalogue of events over the succeeding 12 d resulted in the release of considerable quantities of radioactive material into the environment. Important to the large-scale remediation of the affected areas is the accurate and high spatial resolution characterisation of contamination, including the verification of decontaminated areas. To enable this, a low altitude unmanned aerial vehicle equipped with a lightweight gamma-spectrometer and height normalisation system was used to produce sub-meter resolution maps of contamination. This system provided a valuable method to examine both contaminated and remediated areas rapidly, whilst greatly reducing the dose received by the operator, typically in localities formerly inaccessible to ground-based survey methods. The characterisation of three sites within Fukushima Prefecture is presented; one remediated (and a site of much previous attention), one un-remediated and a third having been subjected to an alternative method to reduce emitted radiation dose.

Potential of aerosolized rifampicin lipospheres for modulation of pulmonary pharmacokinetics and bio-distribution

The aim of the present study was to establish the potential of rifampicin loaded phospholipid lipospheres carrier for pulmonary application. Lipospheres were prepared with rifampicin and phospholipid in the ratio of 1:1 using spray drying method. Further, lipospheres were evaluated for flow properties and surface area measurement. The formulated lipospheres were evaluated in vitro for aerodynamic characterization and in vivo for lung pharmacokinetics and biodistribution studies in Sprague Dawley rats. Powder flow properties finding suggested the free flowing nature of the lipospheres. In-vitro aerosol performance study indicated more than 80±5% of the emitted dose (ED) and 77.61±3% fine particles fraction (FPF). Mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) were found to be 2.72±0.13μm and 3.28±0.12, respectively. In-vitro aerosol performance study revealed the higher deposition at 3, 4 and 5 stages which simulates the trachea-primary bronchus, secondary and terminal bronchus of the human lung, respectively. The drug concentration from nebulized lipospheres in the non-targeted tissues was lesser than from rifampicin-aqueous solution. The pulmonary pharmacokinetic study demonstrated improved bioavailability, longer residence of drug in the lung and targeting factor of 8.03 for lipospheres as compared to rifampicin-aqueous solution. Thus, the results of the study demonstrated the potential of rifampicin lipospheres formulation would be of use as an alternative to existing oral therapy.

Effect of Flow Rate on In Vitro Aerodynamic Performance of NEXThaler® in Comparison with Diskus® and Turbohaler® Dry Powder Inhalers

Background: European and United States Pharmacopoeia compendial procedures for assessing the in vitro emitted dose and aerodynamic size distribution of a dry powder inhaler require that 4.0 L of air at a pressure drop of 4 kPa be drawn through the inhaler. However, the product performance should be investigated using conditions more representative of what is achievable by the patient population. This work compares the delivered dose and the drug deposition profile at different flow rates (30, 40, 60, and 90 L/min) of Foster NEXThaler® (beclomethasone dipropionate/formoterol fumarate), Seretide® Diskus® (fluticasone propionate/salmeterol xinafoate), and Symbicort® Turbohaler® (budesonide/formoterol fumarate).Methods: The delivered dose uniformity was tested using a dose unit sampling apparatus (DUSA) at inhalation volumes either 2.0 or 4.0 L and flow rates 30, 40, 60, or 90 L/min. The aerodynamic assessment was carried out using a Next Generation Impactor by discharging each inhaler at 30, 40, 60, or 90 L/min for a time sufficient to obtain an air volume of 4 L.Results: Foster® NEXThaler® and Seretide® Diskus® showed a consistent dose delivery for both the drugs included in the formulation, independently of the applied flow rate. Contrary, Symbicort® Turbohaler® showed a high decrease of the emitted dose for both budesonide and formoterol fumarate when the device was operated at airflow rate lower that 60 L/min. The aerosolizing performance of NEXThaler® and Diskus® was unaffected by the flow rate applied. Turbohaler® proved to be the inhaler most sensitive to changes in flow rate in terms of fine particle fraction (FPF) for both components. Among the combinations tested, Foster NEXThaler® was the only one capable to deliver around 50% of extra-fine particles relative to delivered dose.Conclusions: NEXThaler® and Diskus® were substantially unaffected by flow rate through the inhaler in terms of both delivered dose and fine particle mass.

Spiromax, a New Dry Powder Inhaler: Dose Consistency under Simulated Real-World Conditions.

Background: Spiromax® is a novel dry powder inhaler for patients with asthma or chronic obstructive pulmonary disease (COPD). The studies presented here provide further data on attributes (in vitro dosing consistency with budesonide–formoterol (DuoResp) Spiromax; flow rates through empty versions of the Spiromax and Turbuhaler inhaler) of importance to patients with asthma or COPD.Methods: Dose-delivery studies were performed using low-, middle-, and high-strength DuoResp Spiromax. Dose consistency was assessed over inhaler life. Total emitted doses (TEDs) were measured at various flow rates, after exposure to high and low temperature or humidity, at different inhaler orientations, and after dropping the inhaler. The criterion for evaluating dose uniformity was whether mean TEDs were within the product specification limits. In separate studies, flow rates were measured after training, using the patient information leaflets, and again after enhanced training as part of a randomized, open-label, cross-over study.Results: Mean values for both budesonide and formoterol were within 85%–115% of the label claim for each strength of DuoResp Spiromax for initial dose uniformity and for the other investigated conditions (temperature, humidity, orientation, dropping, knocking), with the exception of approximately an 80% increase in first dose after dropping the inhaler (subsequent doses not affected). In the flow rate patient study, two patients' inhalations with Spiromax and six with Turbuhaler were <30 L/min. The majority of asthma patients [91% (Spiromax) versus 82% (Turbuhaler)] achieved the preferred flow rate of >60 L/min.Conclusions: DuoResp Spiromax consistently meets dose uniformity criteria, under controlled laboratory conditions and with variations intended to mimic real-world use. Following enhanced training, all patients in the flow study were able to achieve the minimal inspiratory flow rate of >30 L/min, which is required for effective treatment.

Feasibility of highly branched cyclic dextrin as an excipient matrix in dry powder inhalers

We investigated the feasibility of highly branched cyclic dextrin (HBCD) as an excipient matrix in dry powder inhalers (DPIs). The fine particles of HBCD and HBCD/active pharmaceutical ingredients (APIs) were prepared by spray-drying an ethanol-aqueous solution containing HBCD. The particle size of spray-dried HBCD itself was approximately 3.0μm with a wrinkled shape. Solid-state fluorescence emission spectroscopy of 1-naphthoic acid (1-NPA) showed that it was dispersed in a molecular dispersion/solid solution, if the model compound of 1-NPA was spray-dried with HBCD. Powder X-ray diffraction and differential scanning calorimetry indicate that 1-NPA was in the amorphous state after spray-drying with HBCD, which is confirmed by the fluorescence measurements, 1-NPA could be incorporated into HBCD. When the antimycobacterial agent, rifampicin, was spray-dried with HBCD for the purpose of pulmonary administration, the emitted dose and fine-particle fraction of the spray-dried particles of rifampicin with HBCD were 95.7±1.7% and 39.5±5.7%, respectively. The results indicated that HBCD possessed a high potential as an excipient in DPIs, not only by molecular association of API molecules with HBCD, but also by that of API fine crystals.

Novel potential for optimization of antitubercular therapy: Pulmonary delivery of rifampicin lipospheres

The aim of the present work is to develop rifampicin loaded phospholipid lipospheres containing sulfphobutyl ether β-cyclodextrin and Vitamin C for inhalation to test their potential for deep lung delivery. The findings of the solid state characterization revealed the amorphous nature of the lipospheres. These exhibited a better flowability, an aerodynamic diameter in the range of 1.76 to 3.99 µm. Moreover, the fine particle fraction and emitted dose was found in the range of 68.84–83.73% and 80–93%, respectively. Moreover, lipospheres exhibited enhanced/equivalent efficacy in vitro in H37Rv strain. Hence, the results show the potential of lipospheres for pulmonary delivery of rifampicin.

Abstracts from The Aerosol Society Drug Delivery to the Lungs 25Edinburgh International Conference Centre Edinburgh, Scotland, UK December 10–12, 2014

Abstracts from The Aerosol Society Drug Delivery to the Lungs 25Edinburgh International Conference Centre Edinburgh, Scotland, UK December 10–12, 2014

Numerical Analysis of Organ Doses Delivered During Computed Tomography Examinations Using Japanese Adult Phantoms with the WAZA-ARI Dosimetry System.

A dosimetry system for computed tomography (CT) examinations, named WAZA-ARI, is being developed to accurately assess radiation doses to patients in Japan. For dose calculations in WAZA-ARI, organ doses were numerically analyzed using average adult Japanese male (JM) and female (JF) phantoms with the Particle and Heavy Ion Transport code System (PHITS). Experimental studies clarified the photon energy distribution of emitted photons and dose profiles on the table for some multi-detector row CT (MDCT) devices. Numerical analyses using a source model in PHITS could specifically take into account emissions of x rays from the tube to the table with attenuation of photons through a beam-shaping filter for each MDCT device based on the experiment results. The source model was validated by measuring the CT dose index (CTDI). Numerical analyses with PHITS revealed a concordance of organ doses with body sizes of the JM and JF phantoms. The organ doses in the JM phantoms were compared with data obtained using previously developed systems. In addition, the dose calculations in WAZA-ARI were verified with previously reported results by realistic NUBAS phantoms and radiation dose measurement using a physical Japanese model (THRA1 phantom). The results imply that numerical analyses using the Japanese phantoms and specified source models can give reasonable estimates of dose for MDCT devices for typical Japanese adults.

Investigation on the aerosol performance of dry powder inhalation hypromellose capsules with different lubricant levels

HPMC capsules are made by a dipping process and a surface lubricant for the mould pins is an essential processing aid for removing dried capsules shells. For the purpose of this study, the level was determined by quantifying methyloleate (MO) a component found in the lubricant but not in the hypromellose capsules. Here we investigated the influence of the lubricant, low (10.81μg/capsule=60mg/kg MO), medium (15.97μg/capsule=90mg/kg MO) and high (23.23μg/capsule=127mg/kg MO) content on powder (binary mixture of salbutamol: lactose, 1:50 w/w) aerosolization properties was investigated. Results indicated significantly lower emitted dose from capsules with 60mg/kg MO. Furthermore, the 90 and 127mg/kg MO level of lubricant capsules produced almost double the Fine Particle Dose & Fine Particle Fraction compared with the low level of lubricant. The data indicates that lubricant level within capsules has an influence on deposition profiles and amount of drug remaining in capsule and inhaler device after actuation. It is suggested lubricant levels greater than 60mg/kg MO per capsule are required to minimise powder retention within capsules and maximise deposition profiles. AFM (atomic force microscopy) data suggest that internal surface roughness may be related with this phenomena.

High shear mixing of lactose and salmeterol xinafoate dry powder blends: Biopharmaceutic and aerodynamic performances

This work aimed to investigate the effect of a high shear mixer on the biopharmaceutics and aerodynamic performances of salmeterol xinafoate/lactose blends for inhalation. The influence of mixing energy during blending on powder bulk properties, aerosolisation and in vitro dissolution rate of drug was studied. There was a clear dependence of the blends bulk characteristics on the mixing rate and time that affected the emitted dose. The fine particle dose or respirable fraction of salmeterol xinafoate was favored by the mixing intensity leading to the disaggregation of the drug particles. An important dependence of the extra-fine drug particles on the mixing conditions was determined. The effective dispersion on the carrier particles of the salmeterol xinafoate improved the dissolution rate of the drug from the blend. This was due to the drug particle size distribution in the blend. When the fine particle dose of different blends was dissolved, no differences among the dissolution rates were observed.

Pulmonary delivery of antitubercular drugs using spray-dried lipid–polymer hybrid nanoparticles

The present study aimed to develop lipid–polymer hybrid nanoparticles (LPNs) for the combined pulmonary delivery of isoniazid (INH) and ciprofloxacin hydrochloride (CIP HCl). Drug-loaded LPNs were prepared by the double-emulsification solvent evaporation method using the three-factor three-level Box–Behnken design. The optimized formulation had a size of 111.81 ± 1.2 nm, PDI of 0.189 ± 1.4, and PDE of 63.64 ± 2.12% for INH-loaded LPN, and a size of 172.23 ± 2.31 nm, PDI of 0.169 ± 1.23, and PDE of 68.49 ± 2.54% for CIP HCl-loaded LPN. Drug release was found to be sustained and controlled at lower pH and followed the Peppas model. The in vitro uptake study in alveolar macrophage (AM) showed that uptake of the drugs was increased significantly if administered in the form of LPN. The stability study proved the applications of adding PLGA in LPN as the polymeric core, which leads to a much more stable product as compared to other novel drug delivery systems. Spray drying was done to produce an inhalable, dry, powdered form of drug-loaded LPN. The spray-dried (SD) powder was equally capable of producing nano-aggregates having morphology, density, flowability and reconstitutibility in the range ideal for inhaled drug delivery. The nano aggregates produced by spray drying manifested their aerosolization efficiency in terms of the higher emitted dose and fine particle fraction with lower mass median aerodynamic diameter. The in vivo study using pharmacokinetic and pharmacodynamic approaches revealed that maximum internalization efficiency was achieved by delivering LPN in SD powdered forms by pulmonary route.

Spray Dried Aerosol Particles of Pyrazinoic Acid Salts for Tuberculosis Therapy. [Corrected

Tuberculosis is the most serious infectious disease caused by a single organism, Mycobacterium tuberculosis (Mtb). The standard of care is a protracted and complex drug treatment regimen made more complicated and of longer duration by the incidence of multiple and extensively drug resistant disease. Pulmonary delivery of aerosols as a supplement to the existing regimen offers the advantage of delivering high local drug doses to the initial site of infection and most prominent organ system involved in disease. Pyrazinamide is used in combination with other drugs to treat tuberculosis. It is postulated that the action of pyrazinoic acid (POA), the active moiety of pyrazinamide, may be enhanced by local pH adjustment, when presented as a salt form. POA was prepared as leucine (POA-leu) and ammonium salts (POA-NH4), spray dried, and characterized in terms of physicochemical properties (melting point, crystallinity, moisture content), aerodynamic performance (aerodynamic particle size distribution, emitted dose), and in vitro inhibitory effect on two mycobacteria (Mtb and Mycobacterium bovis). Particles were prepared in sizes suitable for inhalation (3.3 and 5.4 μm mass median aerodynamic diameter and 61 and 40% of the aerodynamic particle size distribution less than 4.46 μm, as measured by inertial impaction, for POA-leu and POA-NH4, respectively) and with properties (stoichiometric 1:1 ratio of salt to drug, melting points at ∼180 °C, with water content of <1%) that would support further development as an inhaled dosage form. In addition, POA salts demonstrated greater potency in inhibiting mycobacterial growth compared with POA alone, which is promising for therapy.

Tuning Aerosol Performance Using the Multibreath Orbital® Dry Powder Inhaler Device: Controlling Delivery Parameters and Aerosol Performance via Modification of Puck Orifice Geometry

The current study presents a new approach to tackle high-dose lung delivery using a prototype multibreath Orbital® dry powder inhaler (DPI). One of the key device components is the "puck" (aerosol sample chamber) with precision-engineered outlet orifice(s) that control the dosing rate. The influence of puck orifice geometry and number of orifices on the performance of mannitol aerosols were studied. Pucks with different orifice configurations were filled with 400 mg of spray-dried mannitol and tested in the Orbital® DPI prototype. The emitted dose and overall aerodynamic performance across a number of "breaths" were studied using a multistage liquid impinger. The aerosol performances of the individual actuations were investigated using in-line laser diffraction. The emptying rate of all pucks was linear between 20% and 80% cumulative drug released (R(2) > 0.98), and the amount of formulation released per breath could be controlled such that the device was empty after 2 to 11 breath maneuvers. The puck-emptying rate linearly related to the orifice hole length (R(2) > 0.95). Mass median aerodynamic diameters of the emitted aerosol ranged from 4.03 to 4.62 μm and fine particle fraction (≤6.4 μm) were 50%-66%. Laser diffraction suggested that the aerosol performance and emptying rates were not dependent on breath number, showing consistent size distribution profiles.

Effect of inhalation profile and throat geometry on predicted lung deposition of budesonide and formoterol (BF) in COPD: An in-vitro comparison of Spiromax with Turbuhaler

Successful delivery of inhalation medication to the lungs can be affected by the inhalation manoeuvre used. Conventional in-vitro testing of the emitted dose from a dry powder inhaler (DPI) uses a vacuum pump to simulate an inhalation. We have adapted this method by replacing the pump with patient inhalation profiles and an anatomical throat. Three anatomical throat sizes and three inhalation profiles were used. The profiles represented the 10th, 50th and 90th percentiles of peak inhalation flow and acceleration of flow from a population of 50 COPD patients inhaling through empty Spiromax and Turbuhaler devices. Combining the dose emission results for the three throat sizes, the mean (SD) budesonide fine-particle dose (FPD) from budesonide–formoterol Spiromax 320/9μg was 78.91 (20.18), 79.91 (15.36) and 75.10 (19.91)μg and the total emitted dose (TED) of budesonide was 263.69 (40.74), 261.20 (21.65) and 261.61 (45.65)μg. Similarly, the FPD from 320/9μg Turbuhaler was 22.45 (3.24), 52.20 (12.57) and 69.11 (75.10)μg with a TED of 143.80 (14.90), 149.50 (26.61) and 158.61 (43.04)μg. Spiromax showed greater consistency than Turbuhaler over a range of inspiratory flow profiles. The results demonstrate the value of this new method to assess the doses that patients receive during real-life use of their DPI.

Characterization of a New High-Dose Dry Powder Inhaler (DPI) Based on a Fluidized Bed Design.

The objective of this study was to develop a new high-efficiency dry powder inhaler (DPI) that can effectively aerosolize large masses (25-100 mg) of spray dried powder formulations. The DPI was designed to implement a concept similar to a fluidized bed for aerosolization using small mixing balls made of polytetrafluoroethylene along with a larger, hollow dosing sphere filled with the powder. The performance of the fluidized bed DPI was compared, based on emitted dose (ED) and aerosolization efficiency, to other recently developed capsule-based DPIs that were designed to accommodate smaller powder masses (~2-20 mg). The inhalers were tested with spray dried excipient enhanced growth (EEG) formulations that contained an antibiotic (ciprofloxacin) and hygroscopic excipient (mannitol). The new fluidized bed design produced an ED of 71% along with a mass median aerodynamic diameter of 1.53 μm and fine particle fractions <5 and 1 μm of 93 and 36%, respectively, when used to deliver a 100 mg loaded mass of EEG powder with the advantage of not requiring multiple capsules. Surprisingly, performance of the device was further improved by removing the mixing balls from the inhaler and only retaining the dose containment sphere.