Induction Port Research Articles

Effects of Generation Time on Spray Aerosol Transport and Deposition in Models of the Mouth–Throat Geometry

For most newly developed spray aerosol inhalers, the generation time is a potentially important variable that can be fully controlled. The objective of this study was to determine the effects of spray aerosol generation time on transport and deposition in a standard induction port (IP) and more realistic mouth-throat (MT) geometry. Capillary aerosol generation (CAG) was selected as a representative system in which spray momentum was expected to significantly impact deposition. Sectional and total depositions in the IP and MT geometries were assessed at a constant CAG flow rate of 25 mg/sec for aerosol generation times of 1, 2, and 4 sec using both in vitro experiments and a previously developed computational fluid dynamics (CFD) model. Both the in vitro and numerical results indicated that extending the generation time of the spray aerosol, delivered at a constant mass flow rate, significantly reduced deposition in the IP and more realistic MT geometry. Specifically, increasing the generation time of the CAG system from 1 to 4 sec reduced the deposition fraction in the IP and MT geometries by approximately 60 and 33%, respectively. Furthermore, the CFD predictions of deposition fraction were found to be in good agreement with the in vitro results for all times considered in both the IP and MT geometries. The numerical results indicated that the reduction in deposition fraction over time was associated with temporal dissipation of what was termed the spray aerosol "burst effect." Based on these results, increasing the spray aerosol generation time, at a constant mass flow rate, may be an effective strategy for reducing deposition in the standard IP and in more realistic MT geometries.

Evaluation of the Respimat Soft Mist Inhaler using a Concurrent CFD and In Vitro Approach

The Respimat Soft Mist Inhaler is reported to generate an aerosol with low spray momentum and a small droplet size. However, the transport characteristics of the Respimat aerosol are not well understood. The objective of this study was to characterize the transport and deposition of an aerosol emitted from the Respimat inhaler using a combination of computational fluid dynamics (CFD) modeling and in vitro experiments. Deposition of the Respimat aerosol was assessed in the inhaler mouthpiece (MP), a standard induction port (IP), and a more realistic mouth-throat (MT) geometry at an inhalation flow rate of 30 L/min. Aerosols were generated using an albuterol sulfate (0.6%) solution, and the drug deposition was quantified using both in vitro experiments and a CFD model of the Respimat inhaler. Laser diffraction experiments were used to determine the initial polydisperse aerosol size distribution. It was found that the aerosol generated from the highly complex process of jet collision and breakup could be approximated in the model using effective spray conditions. Computational predictions of deposition fractions agreed well with in vitro results for both the IP (within 20% error) and MT (within 10% error) geometries. The experimental results indicated that the deposition fraction of drug in the MP ranged from 27 to 29% and accounted for a majority of total drug loss. Based on the CFD solution, high MP deposition was due to a recirculating flow pattern that surrounded the aerosol spray and entrained a significant number of small droplets. In contrast, deposition of the Respimat aerosol in both the IP (4.2%) and MT (7.4%) geometries was relatively low. Results of this study indicate that modifications to the current Respimat MP and control of specific patient variables may significantly reduce deposition in the device and may decrease high oropharyngeal drug loss observed in vivo.

The Abbreviated Impactor Measurement (AIM) Concept: Part II—Influence of Evaporation of a Volatile Component—Evaluation with a “Droplet-Producing” Pressurized Metered Dose Inhaler (pMDI)-Based Formulation Containing Ethanol as Cosolvent

The abbreviated impactor measurement (AIM) concept is a potential solution to the labor-intensive full-resolution cascade impactor (CI) methodology for inhaler aerosol aerodynamic particle size measurement. In this validation study, the effect of increasing the internal dead volume on determined mass fractions relating to aerodynamic particle size was explored with two abbreviated impactors both based on the Andersen nonviable cascade impactor (ACI) operating principle (Copley fast screening Andersen impactor [C-FSA] and Trudell fast screening Andersen impactor [T-FSA]). A pressurized metered dose inhaler-delivered aerosol producing liquid ethanol droplets after propellant evaporation was chosen to characterize these systems. Measures of extrafine, fine, and coarse particle mass fractions from the abbreviated systems were compared with corresponding data obtained by a full-resolution ACI. The use of liquid ethanol-sensitive filter paper provided insight by rendering locations visible where partly evaporated droplets were still present when the "droplet-producing" aerosol was sampled. Extrafine particle fractions based on impactor-sized mass were near equivalent in the range 48.6% to 54%, comparing either abbreviated system with the benchmark ACI-measured data. The fine particle fraction of the impactor-sized mass determined by the T-FSA (94.4 +/- 1.7%) was greater than using the C-FSA (90.5 +/- 1.4%) and almost identical with the ACI-measured value (95.3 +/- 0.4%). The improved agreement between T-FSA and ACI is likely the result of increasing the dead space between the entry to the induction port and the uppermost impaction stage, compared with that for the C-FSA. This dead space is needed to provide comparable conditions for ethanol evaporation in the uppermost parts of these impactors.

Comparison of Delivery Characteristics from a Combination Metered-Dose Inhaler Using the Andersen Cascade Impactor and the Next Generation Pharmaceutical Impactor

The purpose of this research was to compare two cascade impaction devices for the aerodynamic particle size assessment of a combination metered-dose inhaler (MDI) product, Combivent. Particle size analysis was performed using an Anderson Mark II cascade impactor (ACI) and a Next Generation Pharmaceutical Impactor (NGI), both fitted with a preseparator and either a 1 L glass chamber or USP throat, and operated at various flow rates. Particle size distributions (PSDs) and dose delivery profiles were assessed by means of the mass median aerodynamic diameter (MMAD), geometric standard deviation (GSD), fine particle fraction <5 micron aerodynamic diameter (FPF(<5 microm)), and induction port deposition fraction (IPF). Under their normal operating conditions, the ACI (28.3 L/min) and the NGI (30 L/min) yield similar PSDs and dose delivery profiles. However, this equivalent performance for the ACI and the NGI no longer exists at a higher flow rate of 60 L/min. Furthermore, changes in PSD results may also be obtained between different operators and/or when different induction port designs were employed. Thus, it is strongly recommended that special care be taken to eliminate variation in experimental parameters and/or selection of ancillary devices such as the preseparator, induction port or throat, to insure good repeatability and reproducibility when testing inhalation drugs.

Comparison of ambient and spray aerosol deposition in a standard induction port and more realistic mouth–throat geometry

For inhalation aerosols, it is well known that spray momentum and geometry characteristics can significantly influence deposition in the mouth–throat (MT) region. However, little is know about the quantitative influence of spray momentum on aerosol transport and deposition. The objective of this study was to evaluate the effect of spray momentum on deposition in a standard induction port (IP) and a representative MT geometry using capillary-generated aerosols. Capillary aerosol generation (CAG) was selected as a model spray aerosol system that has not been previously tested in a realistic throat geometry. To evaluate the effects of spray momentum, the transport and deposition characteristics of transient capillary-generated aerosols were compared with ambient particles of the same size inhaled at a steady flow rate of 30 L/min. To evaluate the influence of geometry, aerosols were considered in a standard IP and a more realistic MT model. A previously tested CFD model was employed to simulate aerosol transport and deposition for ambient and CAG spray aerosols in both the IP and MT geometries. Considering the capillary-generated spray, good agreement was observed for the deposition of drug mass between the in vitro experiments (IP—15.3%, MT—19.4%) and CFD model predictions without droplet evaporation (IP—14.7%, MT—20.8%). In all cases considered, deposition was increased for spray vs. ambient aerosols and in the MT geometry vs. the IP model. Based on CFD results for a representative polydisperse aerosol distribution, the deposition of ambient particles was highly sensitive to the geometry considered, with 2.9 times more deposition in the MT compared to the IP model. In contrast, deposition was less influenced by the geometry for a CAG spray aerosol, with only a 25–40% deposition increase in the MT. As a result, use of the simple IP model may provide a reasonable approximation of total MT deposition for systems with high spray momentum. However, the IP model may be less useful for evaluating the total MT deposition in systems with reduced spray momentum effects.

Aiming for a moving target: Challenges with impactor measurements of MDI aerosols

Experiments were conducted to illustrate some of the challenges associated with measuring dynamic MDI aerosols. Experimental HFA-134a solution MDIs containing 8 or 20% ethanol were measured using the Andersen cascade impactor using three different inlets. It was demonstrated that the size distribution of MDI aerosols changes substantially during the measurement process. The measured size distribution was shown to be dependent on the degree of evaporation that has occurred prior to size measurement. Additionally, the degree of evaporation prior to measurement also influences the number of modes present in the measured size distribution. While MDI aerosols appeared to have a separate large particle mode when measured using the U.S. Pharmacopeial induction port (“USP inlet”; [U.S. Pharmacopeia, 1996. Physical tests and determinations <601> aerosols, metered dose inhalers, and dry powders. Pharmacopeial Forum 22, pp. 3065–3095]), the aerosols were shown to be monomodal when measured using a large volume inlet. The apparent large particle mode observed with the USP inlet seem rather to be droplets from the same monomodal distribution that have not fully evaporated. The complex interaction of the MDI plume and inlet configuration was described. Inlet design was shown to influence inlet deposition, measured particle size, and even deposition in the actuator mouthpiece. Inlet deposition was shown to be highly size-dependent with large droplets being collected more efficiently than smaller droplets.

In Vivo–In Vitro Comparison of Deposition in Three Mouth–Throat Models with Qvar® and Turbuhaler® Inhalers

In vitro polydisperse aerosol deposition in three mouth-throat models, namely, the USP (United States Pharmacopeia) mouth-throat (induction port), idealized mouth-throat, and highly idealized mouth-throat, was investigated experimentally. Aerosol particles emitted from two commercial inhalers, Qvar (pMDI) and Turbuhaler (DPI), were used. The in vitro deposition results in these three mouth-throat models were compared with in vivo data available from the literature. For the DPI, mouth-throat deposition was 57.3 +/- 4.5% for the USP mouth-throat, 67.8 +/- 2.2% for the idealized mouth-throat, and 69.3 +/- 1.1% for the highly idealized mouth-throat, which are all relatively close to the in vivo value of 65.8 +/- 10.1%. In contrast, for the pMDI, aerosol deposition in the idealized mouth-throat (25.8 +/- 4.2%) and the highly idealized mouth-throat (24.9 +/- 2.8%) agrees with the in vivo data (29.0 +/- 18.0%) reported in the literature better than that for the USP mouth-throat (12.2 +/- 2.7%). In both cases, the USP mouth-throat gives the lowest deposition among the three mouth-throat models studied. In summary, both the idealized mouth-throat and highly idealized mouth-throat improve the accuracy of predicted mean in vivo deposition in the mouth-throat region. This result hints at the potential applicability of either the idealized mouth-throat or highly idealized mouth-throat as a future USP mouth-throat standard to provide mean value prediction of in vivo mouth-throat deposition.

Numerical Simulations of Capillary Aerosol Generation: CFD Model Development and Comparisons with Experimental Data

For a capillary aerosol generation system, the mechanisms governing droplet transport from the capillary tip through deposition in an enclosed geometry have not been previously explored. The objective of this study was to develop and validate a CFD model of transport and deposition for capillary-generated albuterol in water aerosols in a standard USP induction port used for pharmaceutical aerosol testing. Within this system, comparisons have been made between experimental measurements and numerical predictions of the jet angle, aerosol deposition in a sectioned induction port model, and size distributions of exiting particles. The CFD model employed accounts for multiscale and multicomponent flow initialized at the 57 μ m capillary tip and extending through the USP induction port with 30 L/min of co-flow air. A discrete Lagrangian particle tracking algorithm with corrections for near-wall anisotropic turbulence has been implemented to model the polydisperse particle phase including the effects of turbulent dispersion and evaporation. Results indicated good agreement between predictions of the numerical model and experimental in vitro measurements. The experimental mean (SD) total mass fraction of drug deposited in the sectioned induction port was 14.6 (1.1)%. Numerical predictions of deposited mass fraction for non-evaporating particles and evaporating droplets were 13.1% and 13.3%, respectively, resulting in relative differences of 10.3% and 8.9%. Comparisons between in vitro measurements and predictions within individual sections of the induction port resulted in relative differences as low at 0.75%. The predicted mass median diameters exiting the induction port for the particle and evaporating droplet models were 3.07 and 3.45 μ m, respectively, in comparison to an experimental value of 3.06 μ m. The numerical model developed in this study can be applied to optimize the capillary aerosol generation process and improve its delivery of aerosols to the lung.

Characterization of Polymeric Micelles for Pulmonary Delivery of Beclomethasone Dipropionate

The potential of using poly-(ethylene oxide)-block-distearoyl phosphatidyl-ethanolamine (mPEG-DSPE) polymer to prepare BDP-loaded micelles with high entrapment efficiency and mass median aerodynamic diameter of less than 5 microm demonstrating sustained release properties was evaluated. The result showed that lyophilized BDP-loaded polymeric micelles with entrapment efficiency of more than 96% could be achieved. Entrapment efficiency was affected by both the drug to polymer molar ratio and the amount of drug used. Investigation using FTIR and DSC confirmed that there was no chemical or physical interaction and the drug was molecularly dispersed within the micelles. TEM images showed that the drug-loaded polymeric micelles were spherical in shape with multivesicular morphology. Further analysis by photon correlation spectroscopy indicated that the particle size of the BDP-loaded micelles was about 22 nm in size. In vitro drug release showed a promising sustained release profile over six days following the Higuchi model. The mass median aerodynamic diameter and fine particle fraction were suitable for pulmonary delivery. Moreover, the small amount of deposited drug in the induction port (throat deposition) suggested possible reduction in incidence of oropharyngeal candidiasis, a side effect normally associated with inhaled corticosteroids therapy. The high encapsulation efficiency, comparable inhalation properties, sustained release behavior together with biocompatibility nature of the polymer support the potential of BDP-loaded polymeric micelles as a versatile delivery system to be used in the treatment of asthma and chronic obstructive pulmonary disease.

Experimental Measurement and Numerical Study of Particle Deposition in Highly Idealized Mouth-Throat Models

Particle deposition in the human mouth-throat is an important factor in evaluating efficiency of drug delivered by inhalation devices, such as pMDIs or DPIs. Current USP standard impactor induction ports (which serve as an in vitro representative of the adult mouth-throat) underpredict in vivo mouth-throat deposition. However, preliminary experimental data in the prototype geometry of a highly idealized mouth-throat has indicated that it is a promising replacement for the USP mouth-throat (Zhang et al. 2004). In this study, partial optimization design of the highly idealized mouth-throat was performed using computational fluid dynamics (CFD) simulations. The performance of six candidate highly idealized mouth-throat geometries, each with a straight tube inlet of inner diameter 17.3 mm, was evaluated experimentally by measuring monodisperse particle deposition efficiency. Gravimetry was used to determine particle deposition in these geometries. Monodisperse particles of di-2-ethylhexyl-sebecate (DEHS) oil ...

Air classifier technology (ACT) in dry powder inhalation: Part 3. Design and development of an air classifier family for the Novolizer ® multi-dose dry powder inhaler

In this study, the design of a multifarious classifier family for different applications is described. The main design and development steps are presented as well as some special techniques that have been applied to achieve preset objectives. It is shown by increasing the number of air supply channels to the classifier chamber (from 2 to 8), that the fine particle losses from adhesion onto the classifier walls can be reduced from 75% to less than 5% of the real dose for soft (spherical) agglomerates. By applying a bypass flow that is arranged as a co-axial sheath of clean air around the aerosol cloud from the classifier, the airflow resistance of the classifier can be controlled over a relatively wide range of values (0.023–0.041 kPa 0.5 min l −1). This, without affecting the fine particle dose or increasing the fine particle losses in the inhaler. Moreover, the sheath flow can be modelled to reduce the depositions in the induction port to the cascade impactor or in the patient's mouth, which are the result of back flows in these regions. The principle of powder induced pressure drop reduction across a classifier enables assessment of the amount of powder in the classifier at any moment during inhalation, from which classifier loading (from the dose system) and discharge rates can be derived. This principle has been applied to study the residence time of a dose in the classifier as function of the carrier size fraction and the flow rate. It has been found that this residence time can be controlled in order to obtain an optimal balance between the generated fine particle fraction and the inhalation manoeuvre of the patient. A residence time between 0.5 and 2 s at 60 l/min is considered favourable, as this yields a high fine particle dose (depending on the type of formulation used) and leaves sufficient inhaled volume for particle transport into the deep lung.

Comparison of Cascade Impaction and Laser Diffraction for Particle Size Distribution Measurements

The Andersen cascade impactor (ACI) and laser diffraction (LD) can be correlated at ambient temperature for aqueous drug formulations atomized by Soft Mist inhalers. A comparison of the two particle size determination methods at different conditions (flow rate, relative humidity) was performed. Under well-defined conditions, the faster LD can substitute the time consuming ACI at least for routine tests. The measurements were performed with three different drug formulations. The aerosol was generated by Soft Mist inhalers, and the droplet distributions were measured simultaneously using a laser diffraction analyzer together with the eight-stage Andersen cascade impactor. The simultaneous measurements ensure that aerosol and air conditions are identical for both LD and ACI. In order to measure the scattered laser light intensity of the aerosol passing the induction port, glass windows were fitted to the induction port. The evaporation effect of the aqueous aerosols on the PSD was investigated at ambient humidity and high humidity (RH > 90%). The simultaneous determination of the droplet size distribution leads to a good correlation between the ACI and LD method only if the measurements were performed at RH of >90%. The humidity of the ambient air had the strongest influence on PSD not only for ACI, but also for LD. In our set-up, the almost saturated air prevents aqueous droplets from drying. The influence of the flow rate on LD was negligible, whereas for ACI, a flow rate dependence is expected. The advantages of LD and the demonstrated compatibility to established EP/USP methods motivate the substitution of the ACI and the use of LD for routine measurements.

Particle characteristics and lung deposition patterns in a human airway replica of a dry powder formulation of polylactic acid produced using supercritical fluid technology.

Polylactic acid (PLA) powders have been used as vector particles to carry pharmaceutical material. Drugs incorporated in the PLA powder can be retained in the lung for a longer period and may be more effective than free-form drugs. A new formulation of L-PLA dry powder, which was easy to disperse in the air, was produced by using a supercritical technology. The L-PLA powder was characterized in terms of physical particle size and aerodynamic size as generated with a Turbuhaler dry powder inhaler (DPI). Electron microscopy analysis of the particles indicated that they were individual particles in bulk form and became aggregate particles after generation by the Turbuhaler. Aerodynamic particle size analysis using both an Aerodynamic Particle Sizer (APS) aerosol spectrometer and Andersen impactor showed that the aerodynamic size decreased as the flow rate in the Turbuhaler increased from 28.3 to 90 L min(-1). Deposition patterns in the human respiratory tract were estimated using a realistic physical replica of human airways. Deposition of the L-PLA was high (80.8%) in the oral airway at 28.3 L min(-1) and an average of 73.4% at flow rates of 60 and 90 L min(-1). In the lung region, the deposition totaled 7.2% at 28.3 L min(-1), 18.3% at 60 L min(-1), and 17.6% at 90 L min(-1). These deposition patterns were consistent with aerodynamic size measurement, which showed 76 to 86% deposition in the USP/EP (US Pharmacopoeia/European Pharmacopoeia) induction port. As the flow rate increased, fewer aggregates were formed resulting in the smaller aerodynamic particles. As a result, more particles penetrated the oral airways and were available for deposition in the lung. Our results showed that L-PLA particles as manufactured by the supercritical technology could be used in a DPI that does not require the use of carrier particles to facilitate aerosol delivery.

Investigation of Some Commercially Available Spacer Devices for the Delivery of Glucocorticoid Steroids from a pMDI

Five commercially available spacers were investigated to determine their influence on the percentage of drug retained in the spacer device, percentage fine particle fraction (FPF), percentage deposited in the induction port, mass median aerodynamic diameter (MMAD), and geometric standard deviation (GSD). Betamethasone valerate (BMV) and triamcinolone acetonide (TAA) were used as model drugs in the pressurized metered dose inhaler (pMDI) formulations containing the propellant HFA 134a. The BMV was dissolved in an ethanol/HFA 134a system, and the TAA was suspended in HFA 134a using ethanol as a dispersing agent. The metering chamber volume of the valve was either 50 μl or 150μl. The spacer devices investigated included the ACE®, Aerochamber®, Azmacort®, Easivent®, and Ellipse® spacers. Each spacer device was attached to an Andersen Cascade Impactor powered by a vacuum pump. Cascade impaction data were used to derive the percentage drug deposited in the induction port, MMAD, GSD, and FPF. The BMV particles emitted from the spacers were finer than the TAA particles because the dissolved drug precipitated as the cosolvent evaporated. The TAA particles had significantly larger MMADs because many undissolved drug particles were contained within each droplet following actuation. After evaporation of the liquid continuous phase, the suspended drug aggregated to form larger agglomerates than those particles precipitated from the BMV pMDI solution droplets. The addition of a spacer device lowered the MMAD to less than 4.7 μm for particles from both the BMV pMDI solution and the TAA pMDI suspension. The addition of a spacer device also lowered the percentage drug deposited in the induction port. The FPF was significantly increased when a spacer device was used. The MMAD significantly decreased when a spacer device was added for the two model drugs when using the 150-μl metering valves, but the difference was not statistically significant when the 50- μl valves were used (P <. 05). The GSD was not influenced by the use of a spacer device. The use of a spacer device will enhance pMDI therapy by reducing the amount of drug deposited in the oropharyngeal region, which will lead to fewer instances of local and systemic side effects. In addition, the spacer devices investigated will allow a higher dose of drug to reach the deep lung, which may permit the use of lower dosage regimens with increased therapeutic efficacy.

An in-vitro assessment of a NanoCrystal™ beclomethasone dipropionate colloidal dispersion via ultrasonic nebulization

Short duration ultrasonic nebulization of a concentrated NanoCrystal™ colloidal dispersion of beclomethasone dipropionate demonstrated an increased respirable fraction and decreased throat deposition when evaluated in an Andersen 8-stage cascade impactor in comparison to the commercially available propellant-based product Vanceril ®. An aqueous-based 1.25% w/w colloidal dispersion of beclomethasone dipropionate when aerosolized via an Omron NE-U03 ultrasonic nebulizer generated a respirable drug dose from 22.6 to 39.4 μg per 2 s actuation period, compared to 12.8 μg for a single actuation of Vanceril ®. When viewed as a percentage of the emitted dose (through the actuator or mouthpiece), the respirable fraction ranged from 56 to 72% for the nanocrystalline formulation versus 36% for the propellant system. In addition, the throat deposition as seen in the induction port was 9–10% of the emitted dose for the novel suspension, as compared to 53% for the commercial product. Thus, when used with the device outlined herein, a nanocrystalline colloidal suspension of beclomethasone dipropionate affords greater potential drug delivery to the conductive airways of the lung in both quantity and as a percent of emitted dose. Additionally, lower potential throat deposition values were observed which may retard the development of undesirable side effects, such as candidiasis, when compared to a propellant based delivery system. Lastly, the ability to atomize aqueous-based nanocrystalline colloidal dispersions represents an environmentally sound alternative to the current chlorofluorocarbon (CFC)-based products and may avoid the technical difficulties of reformulating with chlorine-free propellants.

Comparative study of the in vitro dose delivery and particle size distribution characteristics of an Azmacort metered-dose inhaler in combination with four different spacer devices

This in vitro study compared the dose delivery and particle size distribution performance of triamcinolone acetonide from an Azmacort® metered-dose inhaler (MDI) in combination with four different spacer devices. The four spacer devices studied were the Azmacort® integrated spacer, the AeroChamber®, the InspirEase®, and the Microspacer®. For each MDI/spacer combination, at least two units from each of three lots of Azmacort were used for the determination of dose delivery and particle size distribution. The total delivery of triamcinolone acetonide was assessed using the recently proposed United States Pharmacopeia dosage unit sampling apparatus for MDIs at a flow rate of 60 L/min. Particle size distribution and respirable dose were assessed using the Andersen 1 ACFM Non-viable Ambient Particle Sizing Sampler (Model 20-800). The relative delivery of triamcinolone acetonide from the Azmacort integrated spacer, AeroChamber, InspirEase, and Microspacer, without a delay, was 100%, 72.9%, 16.7%, and 96.6%, respectively. Similarly, dose delivery with a 1-second delay between actuation and sample collection was 33.6%, 12.2%, 20.1%, and 22.9% of the original result, respectively. All the spacers studied changed the particle size distribution of the dose. Each spacer reduced, although not to the same degree, the deposition of triamcinolone acetonide in the throat induction port of the cascade impactor. The highest respirable dose (<5.8 μm) of triamcinolone acetonide was delivered by the Azmacort integrated spacer (68.8%), followed by the Microspacer (51.0%), AeroChamber (50.2%), and InspirEase (11.9%). Thus the Azmacort integrated spacer when used in combination with the Azmacort MDI delivered the highest total dose and greatest respirable dose of triamcinolone acetonide. The differences demonstrated in the performance (dose and particle size) among spacer devices (dose and particle size) in this in vitro study underscore the importance of evaluating drug delivery of all MDI/spacer combinations intended for drug administration. Clinical trials are needed to test the implication of the results that different MDI/spacer combinations may produce variable clinical responses in vivo.

Metered dose inhalers III: metaproterenol sulphate; particle size distribution and dose uniformity

Three American products and one Canadian product were examined for content uniformity and particle size distribution. The results showed that not all products performed equally well. Some of the products exhibited high sprays early in the canister lifetime and all products demonstrated loss of prime. The particle size distributions were determined using the Andersen cascade impactor (USP Induction Port) and the fine particle fraction was determined using the twin impinger. The results showed that three of the four products had similar particle size distribution profiles. Both the Andersen cascade impactor and the twin impinger yielded the same trends in the amount of drug substance delivered to the fine particle fraction.

Metered-dose inhalers. II. Particle size measurement variation

Three apparatuses, the Andersen Cascade Impactor (ACI), the Marple-Miller Impactor (MMI) and the Twin Impinger (TI) were compared in the measurement of particle size distribution (PSD) of four commercially available salbutamol metered-dose inhalers (MDIs). The ACI was fitted with two induction ports. One was that currently described in the United States Pharmacopeia (USP) and the second had a larger volume. Parameters calculated included Mass Median Aerodynamic Diameter (MMAD), Geometric Standard Deviation (GSD) and Fine Particle Dose (FPD). The results demonstrated that several of these parameters were device-dependent and that all of the apparatuses were able to detect differences between some of the MDIs. The larger induction port allowed more drug substance to enter the ACI which may be advantageous in some PSD work.

Piston ring lubrication in a two-stroke diesel engine

Miniature capacitance film thickness transducers were fitted to the cylinder liner of an opposed piston two-stroke diesel engine. The minimum film thickness between the rings and liner was measured and the attitude of the rings as they passed the induction ports was determined.