RESUMEN

Background: Measurement of aerodynamic particle size distribution, a clinically relevant in vitro attribute of inhalable drug products, involves multistage cascade impactors and is tedious and expensive. A leading candidate for a quicker method is the reduced NGI™ (rNGI). This method involves placing glass fiber filters on top of the nozzles of a chosen NGI stage, selected often to collect all particles with an aerodynamic diameter smaller than approximately five microns. These filters contribute additional flow resistance that can alter the flow rate start-up curve, potentially affecting the size distribution and mass of the drug product dispensed by passive dry powder inhalers (DPIs). The magnitude of these additional flow resistance measurements is currently unreported in the literature. Materials and Methods: We placed glass fiber filters on top of the stage 3 nozzles of an NGI, along with the necessary support screen and hold-down ring. We measured the pressure drop across NGI stage 3 with the assistance of a delta P lid and a high-precision pressure transducer. With each filter material type and multiple individual filters, we gathered eight replicates at flow rates of 30, 45, and 60 L/min. Results: The filters typically doubled the total pressure drop through the NGI. For example, at a flow rate of 60 L/min, the Whatman 934-AH filters introduced a pressure drop of about 9800 Pa at stage 3, reducing the absolute pressure exiting the NGI to about 23 kPa below ambient, compared with a typical value of 10 kPa for the NGI alone at this flow rate. Conclusions: The pressure drop across typical filters is approximately equal to that through the NGI alone and therefore will affect the flow start-up rate intrinsic to compendial testing of passive DPIs. This change in start-up rate could cause differences between results of the rNGI configuration and those of the full NGI and will increase the required vacuum pump capacity.

Asunto(s)

RESUMEN

Multiple sources must be consulted to determine the most appropriate procedures for the laboratory-based performance evaluation of aqueous oral inhaled products (OIPs) for the primary measures, dose uniformity/delivery, and aerodynamic particle (droplet) size distribution (APSD). These sources have been developed at different times, mainly in Europe and North America, during the past 25 years by diverse organizations, including pharmacopeial chapter/monograph development committees, regulatory agencies, and national and international standards bodies. As a result, there is a lack of consistency across all the recommendations, with the potential to cause confusion to those developing performance test methods. We have reviewed key methodological aspects of source guidance documents identified by a survey of the pertinent literature and evaluated the underlying evidence supporting their recommendations for the evaluation of these performance measures. We have also subsequently developed a consistent series of solutions to guide those faced with the various associated challenges when developing OIP performance testing methods for oral aqueous inhaled products.

Asunto(s)

RESUMEN

BACKGROUND: SARS-CoV-2 in exhaled aerosols is considered an important contributor to the spread of COVID-19. However, characterizing the size distribution of virus-containing aerosol particles has been challenging as high concentrations of SARS-CoV-2 in exhaled air is mainly present close to symptom onset. We present a case study of a person with COVID-19 who was able to participate in extensive measurements of exhaled aerosols already on the day of symptom onset and then for the following three days. METHODS: Aerosol collection was performed using an eight-stage impactor while the subject was breathing, talking and singing, for 30 min each, once every day. In addition, nasopharyngeal samples, saliva samples, room air samples and information on symptom manifestations were collected every day. Samples were analyzed by RT-qPCR for detection of SARS-CoV-2 RNA. RESULTS: SARS-CoV-2 RNA was detected in seven of the eight particle size fractions, from 0.34 to >8.1 µm, with the highest concentrations found in 0.94-2.8 µm particles. The concentration of SARS-CoV-2 RNA was highest on the day of symptom onset, and declined for each day thereafter. CONCLUSION: Our data showed that 90% of the exhaled SARS-CoV-2 RNA was found in aerosol particles <4.5 µm, indicating the importance of small particles for the transmission of COVID-19 close to symptom onset. These results are important for our understanding of airborne transmission, for developing accurate models and for selecting appropriate mitigation strategies.

Asunto(s)

RESUMEN

This study presents the development and evaluation of a high flow rate gelatin cascade impactor (GCI) to collect different PM particle sizes on water-soluble gelatin substrates. The GCI operates at a flow rate of 100 lpm, and consists of two impaction stages, followed by a filter holder to separate particles in the following diameter ranges: >2.5 µm, 0.2-2.5 µm, and <0.2 µm. Laboratory characterization of the GCI performance was conducted using monodisperse polystyrene latex (PSL) particles as well as polydisperse ammonium sulfate, sodium chloride, and ammonium nitrate aerosols to obtain the particle collection efficiency curves for both impaction stages. In addition to the laboratory characterization, we performed concurrent field experiments to collect PM2.5 employing both GCI equipped with gelatin filter and personal cascade impactor sampler (PCIS) equipped with PTFE filter for further toxicological analysis using macrophage-based reactive oxygen species (ROS) and dithiothreitol consumption (DTT) assays. Our results showed that the experimentally determined cut-point diameters for the first and second impaction stages were 2.4 µm and 0.21 µm, respectively, which agreed with the theoretical predictions. Although the GCI has been developed primarily to collect particles on gelatin filters, the use of a different type of substrate (i.e., quartz) led to similar particle separation characteristics. The findings of the field tests demonstrated the advantage of using the GCI in toxicological studies due to its ability to collect considerable PM-toxic constituents, as corroborated by the DTT and ROS values for the GCI-collected particles which were 26.44 nmoles/min/mg PM and 8813.2 µg Zymosan Units/mg PM, respectively. These redox activity values were more than twice those of particles collected concurrently on PTFE filter using the PCIS. This high-flow-rate impactor can collect considerable amounts of size-fractionated PM on water-soluble filters (i.e., gelatin), which can completely dissolve in water allowing for the extraction of soluble and insoluble PM species for further toxicological analysis.

RESUMEN

Bacterial filtration efficiency is the main characteristic of medical face masks effectivity and quality. The testing method is given by European and US, respectively, standard. The method is based on the analysis of biological aerosol with the bacterium Staphylococcus aureus in Andersen cascade impactor. The Andersen impactor contains six stages simulating the different parts of the respiratory tract, from the upper part with the larger droplets to the lungs with the small aerosol particles of the submicron size. The particles are separated depending on the size and sediment on agar medium in Petri dishes filled in the impactor. The use of the glass Petri dishes is recommended for the Andersen impactor, but the most of laboratories prefer the disposable plastic dishes, actually. The evaluation of the use of plastic dishes in Andersen impactor for the determination of the bacterial filtration efficiency of the medical face masks is the aim of this study.

Asunto(s)

RESUMEN

PURPOSE: Several technical features influencing bronchodilator delivery were evaluated using different vaping drug delivery systems (VDDS). METHODS: Terbutaline in powder form, combined with 1, 3- propanediol used as e-liquid was tested at different concentrations (1 and 2.5 mg/mL), power levels (15 W and 30 W), and set applied resistances (0.15 to 1.5 O) to compare the efficiency of three VDDS (GS AIR2, GS TANK, CUBIS). Samples were collected with a Glass Twin Impinger (GTI). A High Performance Liquid Chromatography (HPLC) was used for drug quantification. The Next Generation Impactor (NGI) measured particle size distribution. Results were also considered with a clinical jet nebulizer (Cirrus TM 2, 2 mL of terbutaline at 2.5 mg/mL). RESULTS: GS AIR2 with resistance = 1.5 O; power = 15 W, and [Terbutaline] = 2.5 mg/mL represents the optimal VDDS conditions to deliver a respirable dose of 20.05 ± 4.2 µg/puff with a mass median aerodynamic diameter (MMAD) of 1.41 ± 0.03 µm. Thus, 52 puffs were required (lasting approximately 15 min of vaping) to reach similar respirable dose and MMAD compared to nebulization. CONCLUSION: We proved that several crucial VDDS technical parameters govern the performance of respiratory bronchodilator delivery including the resistance, power level and atomizer design.

Asunto(s)

RESUMEN

Pediatric patients receiving respiratory support with heated flow nasal cannula (HFNC) systems frequently receive inhaled medications. Most available data have been obtained with vibrating mesh nebulizers that are expensive. Data are lacking regarding the feasibility of using less expensive devices such as continuous output jet nebulizers. The characteristics of the aerosols generated by jet nebulizers operated at different conditions (6 and 9 L/min) were studied alone and connected to a HFNC system and different size cannulas using a cascade impactor and spectrophotometry (276 nm). Aerosol characteristics changed while traveling through the HFNC system. Initial size selection occurred at the exit of the circuit (before connecting to the cannula) with all aerosol <5 µm. Nasal cannula size further selected aerosols and reduced drug delivery. The operating flow of the nebulizer did not affect the delivered mass but higher flows generated smaller particle size aerosols. The addition of supplemental flow significantly reduced the delivered mass. The measured aerosol characteristics would likely result in intrapulmonary deposition. The delivery of aerosolized albuterol generated by a continuous output nebulizer placed in the inlet of a HFNC system and connected to large or XXL cannulas is feasible.

RESUMEN

Pulmonary drug administration provides a platform for the effective local treatment of various respiratory diseases. Application of nano-sized active ingredients results in higher bioavailability because of their large specific surface area. Extra-fine dry powder inhalers reach the smaller airways, further improving therapeutic efficiency. Poorly water-soluble meloxicam was the selected active ingredient. We aimed to decrease the particle size into the nano range by wet milling and producing extra-fine inhalable particles via nano spray-drying. The diameter of the drug was reduced to 138 nm. The particle size of the dry products was between 1.1 and 1.5 µm, and the dispersed diameter was between 500 and 800 nm. Owing to the excipients (poly-vinyl-alcohol, leucine), the spray-dried particles presented nearly spherical morphology. The drug became partially amorphous. Thanks to the improved surface area, the solubility and the released and the diffused amount of the meloxicam increased in artificial lung media. The in vitro aerodynamic measurements showed that the leucine-containing formulations had outstanding fine particle fraction (FPF) deposition with 1.3 µm mass median aerodynamic diameter (MMAD). The aerodynamic particle counter test also proved the extra-fine aerodynamic particle size. The in vitro cell line experiments revealed the non-cytotoxicity of the products and the suppression of the interleukin concentration. Overall, the powders are suitable for deep pulmonary delivery and the local treatment of lung inflammations.

Asunto(s)

RESUMEN

Electronic cigarette, or vaping, products are used to heat an e-liquid to form an aerosol (liquid droplets suspended in gas) that the user inhales; a portion of this aerosol deposits in their respiratory tract and the remainder is exhaled, thereby potentially creating opportunity for secondhand exposure to bystanders (e.g., in homes, automobiles, and workplaces). Particle size, a critical factor in respiratory deposition (and therefore potential for secondhand exposure), could be influenced by e-liquid composition. Hence, the purposes of this study were to (1) test the influence of laboratory-prepared e-liquid composition [ratio of propylene glycol (PG) to vegetable glycerin (VG) humectants, nicotine, and flavorings] on particle size distribution and (2) model respiratory dosimetry. All e-liquids were aerosolized using a second-generation reference e-cigarette. We measured particle size distribution based on mass using a low-flow cascade impactor (LFCI) and size distribution based on number using real-time mobility sizers. Mass median aerodynamic diameters (MMADs) of aerosol from e-liquids that contained only humectants were significantly larger compared with e-liquids that contained flavorings or nicotine (p = 0.005). Humectant ratio significantly influenced MMADs; all aerosols from e-liquids prepared with 70:30 PG:VG were significantly larger compared with e-liquids prepared with 30:70 PG:VG (p = 0.017). In contrast to the LFCI approach, the high dilution and sampling flow rate of a fast mobility particle sizer strongly influenced particle size measurements (i.e., all calculated MMAD values were < 75 nm). Dosimetry modeling using LFCI data indicated that a portion of inhaled particles will deposit throughout the respiratory tract, though statistical differences in aerosol MMADs among e-liquid formulations did not translate into large differences in deposition estimates. A portion of inhaled aerosol will be exhaled and could be a source for secondhand exposure. Use of laboratory-prepared e-liquids and a reference e-cigarette to standardize aerosol generation and a LFCI to measure particle size distribution without dilution represents an improved method to characterize physical properties of volatile aerosol particles and permitted determination of MMAD values more representative of e-cigarette aerosol in situ, which in turn, can help to improve dose modeling for users and bystanders.

Asunto(s)

RESUMEN

Particle size measurement of aerosolized particles from orally inhaled and nasal drug products (OINDPs) can be used to assess the likely deposition distribution in the human respiratory tract (HRT). Size is normally expressed in terms of aerodynamic diameter, since this scale directly relates to the mechanics of particle transport from inhaler to deposition locations. The multistage cascade impactor (CI) is the principal apparatus used to size fractionate aerosols in terms of their aerodynamic particle size distributions (APSDs). Clinically meaningful metrics, such as fine and coarse particle mass fractions, can be determined from the cumulative mass-weighted APSD. In effective data analysis (EDA), CI data are reduced to small and large particle mass. The sum and ratio of these metrics are used to characterize impactor-sized mass, without the need for stage groupings or other APSD interpretation. Aerosol characterization by full-resolution CI is complex, and so, an abbreviated impactor measurement has recently come to prominence. Here, multiple stages of the CI are reduced to just one or two size fractionating stages so that measures of fine (and extrafine) particle mass from a two-stage system can be directly determined without the need to group the mass of active pharmaceutical ingredient (API) on adjacent stages. Time-of-flight-based methods determine APSD more rapidly but require refinements such as single-particle mass spectroscopy to relate size measurements to API content. Alternatives for size characterizing OINDP aerosols are few; laser diffractometry is by far the most important, especially for nasal sprays and solution-based orally inhaled formulations in which there is no confounding of data from suspended excipient(s). Laser-phase Doppler anemometry (L-PDA) has also been shown to be useful for nasal sprays. If aerodynamic size-related information is not a priority, optical microscopy combined with Raman chemical imaging offers prospects for separate determination of API components in combination product-generated aerosols.

Asunto(s)

RESUMEN

The therapeutic benefits of metered dose inhalers (MDIs) in pulmonary disorders are mainly driven by aerosol performance, which depends on formulation variables (drug and excipients), device design, and patient interactions. The present study provides a comprehensive investigation to better understand the effect of formulation variables on mometasone furoate (MF) suspension-based MDI product performance. The effects of MF particle size (volume median diameter; X50) and excipient concentration (ethanol and oleic acid, cosolvent, and surfactant, respectively) on selected critical quality attributes (delivered dose (DD), fine particle dose of particles lesser than 5 µm (FPD < 5), ex-throat dose and median dissolution time (MDT)) were studied. Eight MF-MDI formulations (one per batch) were manufactured based on a reduced factorial design of experiment (DOE) approach, which included relevant formulation levels with varying X50 (1.1 and 2 µm), concentration of ethanol (0.45, 0.9, 1.8, and 3.6%w/w), and oleic acid (0.001 and 0.025%w/w). The in vitro evaluation of these MF-MDI formulations indicated the importance of drug particle's X50, oleic acid, and ethanol canister concentration as critical formulation variables governing the performance of MF suspension-based MDI products. The effect of these formulation variables on DD, FPD < 5, ex-throat dose, and MDT was subsequently utilized to develop empirical relationships linking formulation factors with effects on in vitro performance measures. The developed strategy could be useful for predicting MF-MDI product performance during MDI product development and manufacturing. The systematic DOE approach utilized in this study may provide insights into the understanding of the formulation variables governing the MF-MDI product performance.

Asunto(s)

RESUMEN

In vitro-in vivo correlation is the establishment of a predictive relationship between in vitro and in vivo data. In the context of cascade impactor results of orally inhaled pharmaceutical aerosols, this involves the linking of parameters such as the emitted dose, fine particle dose, fine particle fraction, and mass median aerodynamic diameter to in vivo lung deposition from scintigraphy data. If the dissolution and absorption processes after deposition are adequately understood, the correlation may be extended to the pharmacokinetics and pharmacodynamics of the delivered drugs. Correlation of impactor data to lung deposition is a relatively new research area that has been gaining recent interest. Although few in number, experiments and meta-analyses have been conducted to examine such correlations. An artificial neural network approach has also been employed to analyse the complex relationships between multiple factors and responses. However, much research is needed to generate more data to obtain robust correlations. These predictive models will be useful in improving the efficiency in product development by reducing the need of expensive and lengthy clinical trials.

Asunto(s)

RESUMEN

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of respiratory tract infections in young children. The predominant transmission routes for RSV are still a matter of debate. Specifically, it remains unclear if RSV can be transmitted through the air and what the correlation is between the amount of RSV in nasopharynx samples and in the air. METHODS: The amount of RSV in the air around hospitalized RSV infected infants in single-patient rooms was quantified using a six-stage Andersen cascade impactor that collects and fractionates aerosols and droplets according to size. RSV shedding in the nasopharynx of patients was followed longitudinally by quantifying RSV RNA levels and infectious virus in nasopharyngeal aspirates. Nose and throat swabs of parents and swabs of the patient's bedrail and a datalogger were also collected. RESULTS: Patients remained RSV positive during the air sampling period and infectious virus was isolated up to 9 days post onset of symptoms. In three out of six patients, low levels of RSV RNA, but no infectious virus, were recovered from impactor collection plates that capture large droplets > 7 µm. For four of these patients, one or both parents were also positive for RSV. All surface swabs were RSV-negative. CONCLUSIONS: Despite the prolonged detection of infectious RSV in the nasopharynx of patients, only small amounts of RSV RNA were collected from the air around three out of six patients, which were primarily contained in large droplets which do not remain suspended in the air for long periods of time.

Asunto(s)

RESUMEN

Inhalation route of drug delivery is the most favorable for pulmonary infections wherein direct drug delivery is desired to the lungs. Tuberculosis is one such infection suffering from poor therapeutic efficacy because of low patient compliance due to high drug dosing and lengthy treatment protocols. The current research work was undertaken to develop a dry powder inhaler (DPI) for administration of three first-line antitubercular antibiotics directly to the lungs to improve the treatment rates. Nanoformulations of isoniazid, pyrazinamide, and rifampicin were prepared, spray-dried to obtain a dry powder system, and blended with inhalation grade lactose to develop the DPI. The DPI was evaluated for its flow properties, pulmonary deposition, dissolution profile, and stability. The DPI possessed excellent flow properties with a fine particle fraction of 45% and a mass median aerodynamic diameter of approximately 5 µm indicating satisfactory lung deposition. In vitro drug release exhibited a sustained release of the formulations. In vivo studies showed a prolonged deposition in the lung at elevated concentrations compared to oral therapy. Stability studies proved that the formulation remained stable at accelerated and long-term stability conditions. The DPI could complement the existing oral therapy in enhancing the therapeutic efficacy in patients.

Asunto(s)

RESUMEN

Pulmonary delivery has high bioavailability, a large surface area for absorption, and limited drug degradation. Particle engineering is important to develop inhalable formulations to improve the therapeutic effect. In our work, the poorly water-soluble meloxicam (MX) was used as an active ingredient, which could be useful for the treatment of non-small cell lung cancer, cystic fibrosis, and chronic obstructive pulmonary disease. We aimed to produce inhalable "nano-in-micro" dry powder inhalers (DPIs) containing MX and additives (poly-vinyl-alcohol, leucine). We targeted the respiratory zone with the microcomposites and reached a higher drug concentration with the nanonized active ingredient. We did the following investigations: particle size analysis, morphology, density, interparticular interactions, crystallinity, in vitro dissolution, in vitro permeability, in vitro aerodynamics (Andersen cascade impactor), and in silico aerodynamics (stochastic lung model). We worked out a preparation method by combining wet milling and spray-drying. We produced spherical, 3-4 µm sized particles built up by MX nanoparticles. The increased surface area and amorphization improved the dissolution and diffusion of the MX. The formulations showed appropriate aerodynamical properties: 1.5-2.4 µm MMAD and 72-76% fine particle fraction (FPF) values. The in silico measurements proved the deposition in the deeper airways. The samples were suitable for the treatment of local lung diseases.

RESUMEN

Aerosol sizing is generally measured at ambient air but human airways have different temperature (37°C) and relative humidity (100%) which can affect particle size in airways and consequently deposition prediction. This work aimed to develop and evaluate a new method using cascade impactor to measure particle size at human physiological temperature and humidity (HPTH) taking into account ambient air conditions. A heated and humidified trachea was built and a cascade impactor was heated to 37°C and humidified inside. Four medical aerosols [jet nebulizer, mesh nebulizer, Presurized Metered Dose Inhaler (pMDI), and Dry Powder Inhaler (DPI)] under ambient conditions and at HPTH were tested. MMAD was lower at HPTH for the two nebulizers; it was similar at ambient conditions and HPTH for pMDI, and the mass of particles smaller than 5 µm decreased for DPI at HPTH (51.9 vs. 82.8 µg/puff). In conclusion, we developed a new method to measure particle size at HPTH affecting deposition prediction with relevance. In vivo studies are required to evaluate the interest of this new model to improve the precision of deposition prediction.

RESUMEN

Existing therapies yield low drug encapsulation or accumulation in the lungs, hence the site-specific drug delivery remains the challenge for tuberculosis. Lately, dry powder inhalers (DPIs) are showing promising drug deposition in the deeper lung tissues. Biocompatible polymers with the ability to naturally recognize and bind to the surface receptors of alveolar macrophages, the reservoir of the causative organism, were selected. DPIs comprised of chitosan (CS)/thiolated chitosan (TC) in conjugation with Hyaluronic acid (HA) were synthesized loaded with isoniazid (INH) by using the Design of Experiment (DoE) approach. Nanosuspensions were prepared by ionic gelation method using cross-linker, sodium-tripolyphosphate (TPP) and were optimized by using Box-Behnken 3-level screening design and later freeze-dried to obtain nanopowders. Physico-chemical compatibility of nanoplex systems was investigated using in-vitro characterization techniques. In-vitro release and permeation studies were correlated in terms of the pattern of drug content dissolved over time. In addition, the cytotoxicity studies on A549 cells demonstrated the safety profile of the nanoplexes. Moreover, in-silico studies and aerodynamic profiles verify the suitability of DPIs for further in-vivo tuberculosis therapeutics. DoE analyses affirmed the lack of linearity in the model for the certain response of studied parameters in a holistic way, which was not possible else ways.

Asunto(s)

RESUMEN

An explicit illustration of pulmonary delivery processes (PDPs) was a prerequisite for the formulation design and optimization of carrier-based DPIs. However, the current evaluation approaches for DPIs could not provide precise investigation of each PDP separately, or the approaches merely used a simplified and idealized model. In the present study, a novel modular modified Sympatec HELOS (MMSH) was developed to fully investigate the mechanism of each PDP separately in real-time. An inhaler device, artificial throat and pre-separator were separately integrated with a Sympatec HELOS. The dispersion and fluidization, transportation, detachment and deposition processes of pulmonary delivery for model DPIs were explored under different flow rates. Moreover, time-sliced measurements were used to monitor the PDPs in real-time. The Next Generation Impactor (NGI) was applied to determine the aerosolization performance of the model DPIs. The release profiles of the drug particles, drug aggregations and carriers were obtained by MMSH in real-time. Each PDP of the DPIs was analyzed in detail. Moreover, a positive correlation was established between the total release amount of drug particles and the fine particle fraction (FPF) values (R 2 = 0.9898). The innovative MMSH was successfully developed and was capable of illustrating the PDPs and the mechanism of carrier-based DPIs, providing a theoretical basis for the design and optimization of carrier-based DPIs.

RESUMEN

Multi-stage cascade impactors (CI) are accepted for the determination of metrics of the drug mass aerodynamic particle size distributions (APSD) of aerosols emitted from orally inhaled products (OIPs). This is particularly important for products where the drug to excipient ratio or particle density may not be the same in each aerodynamic size fraction; examples of such products are carrier-containing dry powder inhalers (DPIs) and suspension pressurized metered-dose inhalers (pMDIs). CI measurements have been used as the "gold standard" for acceptance of alternative methods of APSD assessment, such as laser diffraction for nebulized solutions. Although these apparatus are labor-intensive, they are accepted in regulatory submissions and quality control assessments because the mass of active pharmaceutical ingredient(s) in the aerosol can be quantified by chemical assay and measured particle size is based on the aerodynamic diameter scale that is predictive of deposition in the respiratory tract. Two of the most important factors that modify the ideal operation of an impactor are "particle bounce," that is often accompanied by re-entrainment in the air flow passing the stage of interest, and electrostatic charge acquired by the particles during the preparation and aerosolization of the formulation when the inhaler is actuated. This article reviews how both factors can lead to biased APSD measurements, focusing on measurements involving pMDIs and DPIs, where these sources of error are most likely to be encountered. Recommendations are provided for the mitigation of both factors to assist the practitioner of these measurements.

Asunto(s)

RESUMEN

Conventional in vitro tests to assess the aerodynamic particle size distribution (APSD) from inhaler devices use simple right-angle inlets ("mouth-throats", MTs) to cascade impactors, and air is drawn through the system at a fixed flow for a fixed time. Since this arrangement differs substantially from both human oropharyngeal airway anatomy and the patterns of air flow when patients use inhalers, the ability of in vitro tests to predict in vivo deposition of pharmaceutical aerosols has been limited. MTs that mimic the human anatomy, coupled with simulated breathing patterns, have yielded estimates of lung dose from in vitro data that closely match those from in vivo gamma scintigraphic or pharmacokinetic studies. However, different models of MTs do not always yield identical data, and selection of an anatomical MT and representative inhalation profiles remains challenging. Improved in vitro - in vivo correlations (IVIVCs) for inhaled drug products could permit increased reliance on in vitro data when developing new inhaled drug products, and could ultimately result in accelerated drug product development, together with reduced research and development spending.

Asunto(s)