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Biomedical subjects

W H Finlay

Publications and source records attributed to W H Finlay.

18 recordsLinked to original sources
PubMed2006

A dry powder inhaler with reduced mouth-throat deposition.

A novel, compact, and highly efficient dry powder inhaler (DPI) with low mouth-throat deposition is described. The performance of this DPI was evaluated by measuring both (1) the total aerosol deposition in and distal to an idealized mouth-throat cast and (2) the fine particle fraction (FPF) using a standard Mark II Anderson impactor. Ultraviolet (UV) spectroscopy techniques were used in the aerosol deposition measurements. Two inhalation aerosol powders, namely budesonide (extracted from a Pulmicort/Turbuhaler multi-dose device, 200 microg/dose) and ciprofloxacin + lipid + lactose (in-house), were dispersed by the DPI at a steady inhalation flow rate of 60 L/min. The newly developed DPI had a total aerosol delivery distal to the mouth-throat cast of 50.5% +/- 3.04% and 69.7% +/- 1.5% for the budesonide and ciprofloxacin + lipid + lactose aerosols, respectively. This is a significant improvement over the Turbuhaler original device delivery of 34.5% +/- 5.2%, particularly considering that in vitro mouth-throat deposition dropped from 27.5% +/- 5.4% with the budesonide Turbuhaler to 11.0% +/- 3.5% with the present inhaler. The different lung deliveries from the same inhaler for the two formulations above also confirm that the overall performance of an inhaler is optimizable via powder formulations.

Administration, Inhalation↗
PubMed2004

Medical and pharmaceutical nanoengineering conference/International conference on MEMS, nano and smart systems.

Researchers representing all the northern hemispheric continents gathered for 3 days in Banff, Canada, to hear a wide range of talks on the application of micro- and nanotechnology to drug delivery. Topics included nanotubes, nanoparticles, liposomes, micelles, novel inhaled aerosols, antibody engineering and vaccines. Also featured were talks on the application of micro- and nanotechnology to diagnostics, including microfluidics, as well as biomolecular computing. The conference showcased the first demonstration of preliminary concepts for "smart particle aerosols", in which nanofabrication methods are used to produce inhaled aerosol particles with "intelligent" features. The conference provided an excellent forum for cross-fertilisation and discussion between disciplines, with attendees covering a broad range of areas in engineering and the physical and life sciences that are not often found together at a single conference. This breadth of attendees and topics provided a highly stimulating environment. An invitation to next year's conference (24-29 July 2005, Banff, Alberta, Canada) was extended, as listed at the conference website [101].

Drug Delivery Systems↗
PubMed2003

The effect of breathing pattern on nebulizer drug delivery.

The significance of using breathing patterns with simplified functional shapes in vented jet nebulizer research is examined. This study is comprised of three parts: (1) The measurement and analysis of human breathing patterns, (2) the subsequent in vitro testing of the effects of breathing pattern differences using a consistent bench test method, and (3) a computer modeling of these effects on the estimated regional drug deposition in the human lung. Breathing through a Pari LC-Star nebulizer caused statistically significant changes (p < or = 0.05) in measured human breathing patterns when compared to normal breathing. Observed changes included an increase in the tidal volume (34%) and period (39%). Additionally, the average duty cycle shifted 12% towards a more symmetrical breath due to the unequal increase in the inhalation and exhalation times (55% and 28%, respectively). The position of the point of maximum flow in each breath phase shifted towards the beginning and end of the breath for the inhale and exhale by 28% and 48%, respectively. The bench testing revealed that breathing pattern shape variation caused statistically significant differences in nebulizer output only in two cases. Decreasing duty cycles and shifting the point of maximum flow towards the beginning of the breath both result in a decrease in output efficiency. Square flow patterns produced slight but consistently higher output efficiencies (average 2.1% higher) and a constant output particle size over the course of each breath, different from the other non-square patterns. Numerical simulations revealed no significant dosage differences resulting from breathing pattern shape variations. However, square wave patterns consistently produced slight overpredictions in comparison with real nebulizer patterns. In contrast, sine wave patterns were found to produce essentially the same results as nebulizer patterns in both the bench tests and in the deposition simulations. This suggests that sine wave shapes are preferable for simulating breathing when bench testing drug delivery using vented jet nebulizers.

Adult↗
PubMed2001

In vitro aerosol delivery and regional airway surface liquid concentration of a liposomal cationic peptide.

A liposome encapsulation was optimized for the entrapment and aerosol delivery of an alpha-helical cationic peptide, CM3, which had shown good antimicrobial and antiendotoxin activity in vitro. The encapsulation procedure and the phospholipids used were selected to maximize both the encapsulation and nebulization efficiencies, without compromising liposomal integrity during nebulization. The best compromise was found with dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol (3:1 molar ratio), which allowed for peptide encapsulation levels of 730 microg/mL using 30 mM lipid concentration. The aerosol produced with the selected liposomal formulation was subsequently analyzed for determination of size distribution and nebulizer efficiencies. These quantities were used as input for a mathematical lung deposition model, which predicted local lung depositions of the liposomal peptides for three models of lung geometry and breathing patterns: an adult, an 8-year-old child, and a 4-year-old child. The deposition results were then applied to a novel model of airway surface liquid in the lung to assess the concentration of the deposited peptide. The resulting concentration estimates indicate that the minimum inhibitory levels of CM3 can be reached over most part of the tracheobronchial region in the adult model, and can be exceeded throughout the same region in both pediatric model subjects, using a valved jet nebulizer with a 2.5mL volume fill.

Adult↗
PubMed2001

In vitro monodisperse aerosol deposition in a mouth and throat with six different inhalation devices.

Experiments were performed to determine the effect of different pharmaceutical aerosol inhalation devices on the deposition of monodisperse aerosols in an idealized mouth and throat geometry. The devices included two dry powder inhalers (Diskus and Turbuhaler), two nebulizers (Pari LC STAR and Hudson T-Updraft), and a metered dose inhaler with attached holding chamber (Aerochamber), in addition to a straight tube (1.7 cm inner diameter). Aerosol particles (DL-alpha tocopheryl acetate) of diameters of 2.5, 5, and 7 microm generated by a vibrating orifice generator were inhaled at steady air flow rates of Q = 5-90 L/min through the devices and into the mouth-throat. Deposition in the mouth-throat and after-filter were determined by ultraviolet (UV) spectrophotometric assay. The amount of deposition in the mouth and throat region was found to depend on the type of device that the aerosol entered through. Deposition in the extrathoracic region with the two types of jet nebulizers did not differ significantly (p > 0.1) from that of a straight tube or each other over their entire tested range of 590 > or = pd2Q > or = 11,375, where p is particle density (in g/cm3), d is particle diameter (in microm), and Q is flow rate (in cm3/s). The metered dose inhaler with attached holding chamber was found to differ from the straight tube only at two intermediate values of pd2Q = 5,145 and 16,033. The deposition occurring for the dry powder inhalers was found to be significantly greater than for the straight tube for all values of pd2Q > or = 10,954 for the Diskus and pd2Q > or = 9,435 for the Turbuhaler. Deposition with the dry powder inhalers was found to be up to 14 times greater than that with the straight tube. Thus, the inhaler geometry that the aerosol passes through prior to entering the mouth and throat region can greatly affect the deposition in the mouth-throat.

Aerosols↗
PubMed2000

Inertial sizing of aerosol inhaled from two dry powder inhalers with realistic breath patterns versus constant flow rates.

A procedure is developed that allows particles inhaled with realistic breath patterns to be sized by cascade impaction at a constant flow rate. This procedure is then used to examine the difference between particle sizes obtained with constant flow rate (step profile) versus actual-subject breath patterns for two dry powder inhalers DPIs: the Ventodisk and Spiros inhalers (delivering salbutamol sulphate). Aerosol inhaled from the DPIs by a breath simulator was combined with make-up air to provide 300 l/min. to a pair of virtual impactors. These impactors separate out particles in the nominal diameter range of 1-10 microm for sizing at 30 l/min. by a MOUDI cascade impactor, with filter collection of particles outside this range. Breathing patterns of ten subjects ranging in age from 6 to 17 years of age were measured and recorded using whole-body plethysmography while these volunteers inhaled through Ventodisk and Spiros inhalers. Particle sizes with four of these breath patterns, as well as several constant flow rate step profiles, were then obtained using the sizing apparatus with a realistic mouth throat intake. Our results show that as long as the constant flow rates were near typical values occurring in the actual-subject breaths, particle sizes obtained with constant flow rates were not significantly different (P > 0.01) from those occurring with actual-subject breath patterns. Significant differences are present if constant flow rates unrepresentative of those expected during particle uptake with the actual-subject patterns are used with the Ventodisk. These results show that judiciously chosen constant flow rates give rise to inertial particle size measurements that are equivalent to those obtained during actual-subject inhalation for the two types of DPIs tested.

Adolescent↗
PubMed2000

Mapping PET-measured triamcinolone acetonide (TAA) aerosol distribution into deposition by airway generation.

The three dimensional (3D) distribution of inhaled drugs was measured using Positron Emission Tomography (PET) (Berridge, M.S, Muswick, G.J., Lee, Z., Leisure, G.L., Nelson, A.D., Muzic, R.F. Jr., Miraldi, F., Heald, D.L., 1997. PET evaluation of Azmacort(R) ([C-11]triamcinolone acetonide) dose administration. J. Nucl. Med. 38 (5) Suppl., 4-5). Data analysis was based upon regional ratios or penetration indices. To improve the analytical usefulness and objectivity, labeled drug from dynamic PET images was mapped into 23 airway generations following a general framework from a SPECT-based methodology (Fleming, J.S., Nassim, M.A., Hashish, A.H., Bailey, A.G. , Conway, J., Holgate, S., Halson, P., Moore, E., Martonen, T.B., 1995. Description of pulmonary deposition of radiolabeled aerosol by airway generation using a conceptual three dimensional model of lung morphology. J. Aerosol Med. 8, 341-356). A recently developed airway network model was used in this study. Quantitative PET scans of [C-11]triamcinolone acetonide distribution in the lung were determined following administration of Azmacort(R), a commercial metered dose inhaler with an integrated spacer device. Distributions at varying time periods after drug administration were investigated to explore the dynamics and kinetics of the aerosolized drug. Initially, deposition of labeled drug on conducting airways (generations 1-14) was found to be higher than those on acinar airways (generation 15-23), 64% versus 36%. The distribution pattern changed slowly with time. By 47 min, 51% of the dose remaining in the lung was found on conducting airways while 49% was on acinar airways. This study illustrates the value of PET imaging for the evaluation and design of drug formulations.

Aerosols↗
PubMed2000

Validating deposition models in disease: what is needed?

To develop theoretical deposition models, assumptions are introduced to make the models computationally affordable. For this reason, experimental (in vivo) validation of such models is needed to give confidence to the assumptions being made. However, for an in vivo deposition experiment to be considered useful for validation of a model, a number of parameters must be measured in the experiment for input to the model. Ideally, these parameters would include time-dependent breathing flow rates during aerosol exposure, properties of the inhaled aerosol as a function of time during the breath (including particle size distribution, aerosol mass fraction, as well as hygroscopic properties, inhaled temperature and humidity if hygroscopicity is important), in addition to anatomical regional deposition data and detailed lung geometry measurements. Furthermore, because of the dependence of extrathoracic filtering on the inlet conditions at the mouth and the complexity of modeling deposition in this region, experimental data on the filtering properties of the mouth-throat are needed. Although some of the above parameters are impractical to measure with current experimental techniques, it would greatly aid the development of deposition models if as many of these parameters as possible were measured in future in vivo deposition experiments. Data exemplifying the importance of measuring the above parameters is discussed.

Aerosols↗
PubMed2000

Lung delivery of aerosolized dextran.

The ability of nebulizers to deliver dextran (nominal molecular mass, 4,000 g/mol) to the lung as an inhaled aerosol is evaluated by in vitro experimental methods and mathematical models. Dextran in isotonic saline was aerosolized by four nebulizer types (Pari LC STAR, Hudson T-Updraft II, Acorn II, and Sonix 2000) at dextran concentrations </= 400 mg/ml and with 2.5- and 4-ml volume fills. Aerosols inhaled during breath simulation were characterized by in-line phase Doppler anemometry, filter collection, osmometry, and gravimetry. Mathematical models were used to estimate amounts of the characterized aerosols depositing in the different regions of lung models, and mathematical models of mucous thickness were then developed to estimate initial concentrations of the depositing dextran in the mucus of each conducting airway generation. Models of three subjects (4 yr old, 8 yr old, and adult) were used. The high viscosity of the dextran solutions tested (up to seven times that of water) negatively impacts nebulization, and results in poor performance with most delivery systems tested. Our results suggest that airway mucosal dextran concentrations associated with efficacy in previous animal and in vitro models are achievable with reasonable delivery times (</= 12 min) with only one of the delivery systems/formulations tested: the Pari LC STAR nebulizer, using a 2. 5-ml volume fill and a dextran concentration of 200 mg/ml.

Administration, Inhalation↗
PubMed2000

Overcoming the adverse effect of humidity in aerosol delivery via pressurized metered-dose inhalers during mechanical ventilation.

The well-known problem of reduced drug delivery that occurs when heated, humid air is used with pressurized metered-dose inhalers (pMDIs) and spacers in intubated settings is carefully studied with Airomir using an in vitro model under controlled conditions of temperature and humidity. A better understanding of the physical processes leading to the aforementioned drop in performance is obtained, and a method is devised to circumvent the problem without having to reduce the temperature or humidity of the ventilator circuit. The present study shows that the mole fraction of water vapor in the ventilation air (and not the temperature) is the major factor behind the sharp drop in the amount of drug delivered to the lung. However, the presence of water vapor does not affect performance because of hygroscopic growth. Instead, it influences the initial atomization process and the early stages of aerosol generation. Removal of these negative effects can be achieved by using a larger spacer that allows longer times for the aerosol to evaporate, as is demonstrated in the present study.

Aerosols↗
PubMed1999

In vitro comparison of salbutamol hydrofluoroalkane (Airomir) metered dose inhaler aerosols inhaled during pediatric tidal breathing from five valved holding chambers.

Amounts of salbutamol delivered from chlorofluorocarbon (CFC)-free metered dose inhalers (MDIs) (Airomir; 3M, St. Paul, MN) in particle sizes appropriate for inhalational treatment with five common holding chambers (NES [or Nebuchamber] spacer [Astra Draco AB, Lund, Sweden], AeroChamber [Trudell Medical, London, Ontario, Canada], OptiChamber [Health-scan Products, Cedar Grove, NJ], Vent170 spacer [Nordac Design, Waterloo, Ontario, Canada], and E-Z Spacer [WE Pharmaceuticals, Ramona, CA]) when used under simulated pediatric tidal breathing conditions were determined. Five devices of each type were tested with Airomir hydrofluoroalkane (HFA) inhalers (100 micrograms of salbutamol). Each device was connected to face replicas representative of 7-month-old (infant) and 2-year-old (toddler) children, and aerosol was also inhaled into an Andersen cascade impactor (Graseby Andersen, Smyrna, GA) using a valve system and simulated tidal breathing patterns representative of children of these ages. Amounts of drug inhaled in fine particles with the HFA formulation are significantly less (up to 46% less) with the E-Z Spacer (P < 0.01) compared with amounts inhaled in previous studies with the CFC formulation but are nearly the same with other holding chamber types (e.g., differing by < 6% for the AeroChamber). With the HFA formulation, the metal NES spacer delivered significantly more salbutamol in fine particles (P < 0.01) than any of the other holding chambers. Amounts of salbutamol inhaled in fine particles during pediatric tidal breathing from valved holding chambers with Airomir varies considerably between holding chamber types.

Aerosols↗
PubMed1998

Estimating the type of hygroscopic behavior exhibited by aqueous droplets.

A method that allows hygroscopic aerosol behavior to be classified into three types based on the values of the two nondimensional parameters gamma and zeta is presented. Both parameters can be estimated relatively simply, allowing prediction of the type of behavior a hygroscopic aerosol is likely to exhibit. The parameter gamma is the ratio of the mass of droplets per unit volume divided by the mass of vapor per unit volume that must be exchanged between the droplets and the surrounding air in order to reach equilibrium. The parameter zeta is a measure of the importance of hygroscopic size changes if the aerosol were to be treated as a single droplet. Under many circumstances, zeta is large enough that aerosol behavior is determined solely by gamma. In this case, hygroscopic size changes are negligible if gamma is greater than approximately 3. In contrast, if gamma is less than approximately 0.1, hygroscopic size changes are significant but can be treated using a classical one-way coupled approach. For other values of gamma, hygroscopic size changes require a two-way coupled treatment to predict accurately. Values of gamma and zeta are estimated for several hygroscopic aerosols whose behavior is given in the literature, and it is found that these aerosols to classify into the above categories according to gamma and zeta.

Aerosols↗
PubMed1998

In vitro comparison of beclomethasone and salbutamol metered-dose inhaler aerosols inhaled during pediatric tidal breathing from four valved holding chambers.

STUDY OBJECTIVES: To determine the amount of salbutamol or beclomethasone delivered from metered-dose inhalers (MDIs) in particle sizes appropriate for inhalational treatment with four common holding chambers (AeroChamber, OptiChamber, Space Chamber, E-Z Spacer) when used under simulated pediatric tidal breathing conditions. DESIGN: Five devices of each type were tested with salbutamol (100 microg, Glaxo-Wellcome) and beclomethasone (50 microg, Glaxo-Wellcome) MDIs. Each device was connected to face replicas representative of 7-month-old (infant), 2-year-old (toddler), and 4-year-old (child) children and aerosol inhaled into a cascade impactor (Anderson) using a valve system and simulated tidal breathing patterns representative of children of these ages. MEASUREMENTS AND RESULTS: Amounts of drug inhaled in fine particles varied significantly between devices and ages (p < 0.01), eg, for beclomethasone, from 4 microg (infant, Space Chamber) to 8 microg (toddler, OptiChamber), and for salbutamol, from 18 to 36 microg. The AeroChamber and OptiChamber behaved quite similarly, delivering more drug in the fine particles than the other two devices, and having insignificant variations in these amounts with age (p > 0.05). CONCLUSIONS: Amounts of drug inhaled in fine particles during pediatric tidal breathing from valved holding chambers are dependent on the holding chamber model, the drug used, and the breathing pattern, although dependence on the breathing pattern is relatively small for some of the devices tested.

Administration, Inhalation↗
PubMed1996

Regional deposition of inhaled hygroscopic aerosols: in vivo SPECT compared with mathematical modeling.

The regional deposition patterns of inhaled hygroscopic aerosols obtained in vivo in the studies of Phipps et al. (P. R. Phipps, I. Gonda, D. L. Bailey, P. Borham, G. Bautovich, and S. D. Anderson. Am. Rev. Respir. Dis. 139: 1516, 1989; and P. R. Phipps, I. Gonda, S. D. Anderson, D. L. Bailey, and G. Bautovich. Eur. Respir. J. 7: 1474-1482, 1994) and Chan et al. (H.-K. Chan, P. R. Phipps, I. Gonda, P. Cook, R. Fulton, I. Young, and G. Bautovich. Eur. Respir. J. 7: 1483-1489, 1994) by using single-photon-emission computerized tomography (SPECT) are compared with the regional deposition predicted by the hygroscopic lung deposition model of Finlay and Stapleton (W. H. Finlay and K. W. Stapleton. J. Aerosol Sci. 26: 655-670, 1995). Three pairs of saline aerosols are considered: isotonic with small [2.6-microns mass median aerodynamic diameter (MMAD), geometric standard deviation (GSD) 1.4] vs. large (5.5-microns MMAD, GSD 1.7) droplets; hypotonic (0.3% NaCl) vs. hypertonic (4.5% NaCl) with 3.7- to 3.8-microns MMAD (GSD 1.4), and hypotonic vs. hypertonic (3.7- to 3.8-microns MMAD, GSD 1.5-1.8) with reduced number of droplets per cubic centimeter. For each of the three pairs of aerosols, no significant difference (P > 0.05) was found between the in vivo and computational results for either the mean value or the variance of the difference in peripheral to central deposition. Thus it appears that theoretical calculations can be used to predict the pattern of lung deposition of hygroscopic aerosols in populations of normal subjects.

Administration, Inhalation↗
PubMed1994

An in vitro method for determining regional dosages delivered by jet nebulizers.

A methodology for determining the regional dosages delivered to the respiratory tract by a jet nebulizer is presented and applied to the DeVilbiss PulmoNeb disposable nebulizer delivering a 2.5 ml nebule of Ventolin (1 mg/ml salbutamol sulphate). Results are obtained both with tapping of the nebulizer, which enhances nebulizer performance, and without tapping. The nebulizer output is characterised by measuring the total mass and the mass of solids leaving the nebulizer per minute, and performing a control volume analysis of the nebulizer. Particle size distributions are determined by phased Doppler anemometry. Deposition probabilities are calculated using a semi-empirical model for the deposition of hygroscopic aerosol particles in healthy adult Caucasian males. Deposition probabilities are then converted to regional dosages using the measured nebulizer output characteristics. The regional dosages (% of initial dose in nebulizer) of Ventolin delivered to the extrathoracic, bronchial, and alveolar regions of the respiratory tract are 0.248 +/- 0.005 mg (9.9%), 0.034 +/- 0.001 mg (1.4%), and 0.071 +/- 0.002 mg (2.8%) respectively when the nebulizer was tapped during operation, and 0.184 +/- 0.005 mg (7.4%), 0.025 +/- 0.001 mg (1.0%), and 0.052 +/- 0.002 mg (2.1%) when tapping was not used. This methodology provides a well controlled and rapid means of comparing the effectiveness of different nebulizers for use in aerosol therapy.

Adult↗