The Experts below are selected from a list of 837 Experts worldwide ranked by ideXlab platform

P. Worth Longest - One of the best experts on this subject based on the ideXlab platform.

  • Initial Development of an Air-Jet Dry Powder Inhaler for Rapid Delivery of Pharmaceutical Aerosols to Infants
    Journal of aerosol medicine and pulmonary drug delivery, 2020
    Co-Authors: Connor Howe, Michael Hindle, Serena Bonasera, Vijaya Krishna Rani, P. Worth Longest
    Abstract:

    Background: Positive-pressure dry powder inhalers (DPIs) have recently been developed that in combination with highly dispersible spray-dried powder formulations can achieve high efficiency aerosolization with low actuation air-volumes (AAVs). The objective of this study was to initially develop the positive-pressure air-jet DPI platform for high efficiency aerosol delivery to newborn infants by using the nose-to-lung route. Methods: Aerosolization performance metrics of six air-jet DPIs were first assessed at AAVs that were consistent with full-term (30 mL) and preterm (10 mL) neonates. Designs of the air-jet DPIs varied based on geometry of the inlet and outlet flow passages and shape of the aerosolization chamber. Aerosolization metrics evaluated at the device outlet were emitted dose (ED) and mass median aerodynamic diameter (MMAD). Designs with the best aerosolization performance were connected to a smoothly expanding nasal interface and full-term infant (3550 g) nose-throat (NT) model with tracheal filter. Results: The three best performing devices had characteristics of a cylindrical and horizontal aerosolization chamber with a flush or protruding outlet orifice. Including multiple air inlets resulted in meeting the aerosolization targets of >80% ED (based on loaded dose) and MMAD

  • Application of an inline dry powder inhaler to deliver high dose Pharmaceutical Aerosols during low flow nasal cannula therapy.
    International journal of pharmaceutics, 2018
    Co-Authors: Dale Farkas, Michael Hindle, P. Worth Longest
    Abstract:

    Abstract Inline dry powder inhalers (DPIs) offer a potentially effective option to deliver high dose inhaled medications simultaneously with mechanical ventilation. The objective of this study was to develop an inline DPI that is actuated using a low volume of air (LV-DPI) to efficiently deliver Pharmaceutical Aerosols during low flow nasal cannula (LFNC) therapy. A characteristic feature of the new inline LV-DPIs was the use of hollow capillary tubes that both pierced the capsule and provided a pathway for inlet air and exiting aerosol. Aerosolization characteristics, LFNC depositional losses and emitted dose (ED) were determined using 10 mg powder masses of a small-particle excipient enhanced growth (EEG) formulation. While increasing the number of inlet capillaries from one to three did not improve performance, retracting the inlet and outlet capillaries did improve ED by over 30%. It was theorized that high quality performance requires both high turbulent energy to deaggregate the powder and high wall shear stresses to minimize capsule retention. Best case performance included a device ED of approximately 85% (of loaded dose) and device emitted mass median aerodynamic diameter of 1.77 µm. Maximum ED through the LFNC system and small diameter (4 mm) nasal cannula was approximately 65% of the loaded dose. Potential applications of this device include the delivery of high dose inhaled medications such as surfactants, antibiotics, mucolytics, and anti-inflammatories.

  • In Vitro Assessment of Small Charged Pharmaceutical Aerosols in a Model of a Ventilated Neonate
    Journal of aerosol science, 2017
    Co-Authors: Landon Holbrook, Michael Hindle, P. Worth Longest
    Abstract:

    Aerosolized medications may benefit infants receiving mechanical ventilation; however, the lung delivery efficiency of these Aerosols is unacceptably low. In vitro experiments were conducted to evaluate aerosol delivery through conventional and modified ventilation systems to the end of a 3mm endotracheal tube (ETT) under steady state and realistic cyclic flow conditions. System modifications were employed to investigate the use of small charged particles and included streamlined components, a reduction in nebulizer liquid flow rate, synchronization with inspiration, and implementation of a previously designed low-flow induction charger (LF-IC), which was further modified in this study. Cyclic flow experiments implemented a modern ventilator with bias airflow and an inline flow meter, both of which are frequently excluded from in vitro tests but included in clinical practice. The modified LF-IC system demonstrated superior delivery efficiency to the end of the ETT (34%) compared with the commercial system (~1.3%) operating under cyclic ventilation conditions. These findings indicate that commercial systems still provide very low lung delivery efficiencies despite decades of innovation. In contrast, the modified system increased dose delivery to the end of the ETT by 26-fold. Despite initial concerns, the charged aerosol could be efficiently delivered through the small diameter ETT and reach the lungs. Future studies will be required to determine if the applied particle charge can eliminate expected high exhalation aerosol loss and will require the development of a realistic lung model.

  • Absorption and Clearance of Pharmaceutical Aerosols in the Human Nose: Effects of Nasal Spray Suspension Particle Size and Properties
    Pharmaceutical Research, 2016
    Co-Authors: Alex D. Rygg, Michael Hindle, P. Worth Longest
    Abstract:

    Purpose The objective of this study was to use a recently developed nasal dissolution, absorption, and clearance (DAC) model to evaluate the extent to which suspended drug particle size influences nasal epithelial drug absorption for a spray product. Methods Computational fluid dynamics (CFD) simulations of mucociliary clearance and drug dissolution were used to calculate total and microscale epithelial absorption of drug delivered with a nasal spray pump. Ranges of suspended particle sizes, drug solubilities, and partition coefficients were evaluated. Results Considering mometasone furoate as an example, suspended drug particle sizes in the range of 1-5 μm did not affect the total nasal epithelial uptake. However, the microscale absorption of suspended drug particles with low solubilities was affected by particle size and this controlled the extent to which the drug penetrated into the distal nasal regions. Conclusions The nasal-DAC model was demonstrated to be a useful tool in determining the nasal exposure of spray formulations with different drug particle sizes and solubilities. Furthermore, the model illustrated a new strategy for topical nasal drug delivery in which drug particle size is selected to increase the region of epithelial surface exposure using mucociliary clearance while minimizing the drug dose exiting the nasopharynx.

  • Absorption and Clearance of Pharmaceutical Aerosols in the Human Nose: Development of a CFD Model.
    Journal of aerosol medicine and pulmonary drug delivery, 2016
    Co-Authors: Alex D. Rygg, P. Worth Longest
    Abstract:

    Abstract Purpose: The objective of this study was to develop a computational fluid dynamics (CFD) model to predict the deposition, dissolution, clearance, and absorption of Pharmaceutical particles in the human nasal cavity. Methods: A three-dimensional nasal cavity geometry was converted to a surface-based model, providing an anatomically-accurate domain for the simulations. Particle deposition data from a commercial nasal spray product was mapped onto the surface model, and a mucus velocity field was calculated and validated with in vivo nasal clearance rates. A submodel for the dissolution of deposited particles was developed and validated based on comparisons to existing in vitro data for multiple Pharmaceutical products. A parametric study was then performed to assess sensitivity of epithelial drug uptake to model conditions and assumptions. Results: The particle displacement distance (depth) in the mucus layer had a modest effect on overall drug absorption, while the mucociliary clearance rate was f...

Michael Hindle - One of the best experts on this subject based on the ideXlab platform.

  • initial development of an air jet dry powder inhaler for rapid delivery of Pharmaceutical Aerosols to infants
    Journal of Aerosol Medicine and Pulmonary Drug Delivery, 2021
    Co-Authors: Connor Howe, Michael Hindle, Serena Bonasera, Vijaya Krishna Rani, Worth P Longest
    Abstract:

    Background: Positive-pressure dry powder inhalers (DPIs) have recently been developed that in combination with highly dispersible spray-dried powder formulations can achieve high efficiency aerosolization with low actuation air-volumes (AAVs). The objective of this study was to initially develop the positive-pressure air-jet DPI platform for high efficiency aerosol delivery to newborn infants by using the nose-to-lung route. Methods: Aerosolization performance metrics of six air-jet DPIs were first assessed at AAVs that were consistent with full-term (30 mL) and preterm (10 mL) neonates. Designs of the air-jet DPIs varied based on geometry of the inlet and outlet flow passages and shape of the aerosolization chamber. Aerosolization metrics evaluated at the device outlet were emitted dose (ED) and mass median aerodynamic diameter (MMAD). Designs with the best aerosolization performance were connected to a smoothly expanding nasal interface and full-term infant (3550 g) nose-throat (NT) model with tracheal filter. Results: The three best performing devices had characteristics of a cylindrical and horizontal aerosolization chamber with a flush or protruding outlet orifice. Including multiple air inlets resulted in meeting the aerosolization targets of >80% ED (based on loaded dose) and MMAD <1.8 μm. Reducing the AAV by a factor of threefold from 30 to 10 mL had little effect on aerosol formation. The three leading devices all delivered ∼50% of the loaded dose through a full-term NT in vitro model by using an AAV of 30 mL. Conclusion: With careful selection of design attributes, the air-jet DPI platform is capable of high-efficiency aerosolization of a 10 mg powder mass by using AAVs that are consistent with infant inhalation. The associated infant air-jet DPI system, which forms a seal at the nostril(s) and delivers both the aerosol and a complete inhalation, is capable of rapid and efficient aerosol administration to infant lungs, based on initial testing in a full-term in vitro NT model.

  • Initial Development of an Air-Jet Dry Powder Inhaler for Rapid Delivery of Pharmaceutical Aerosols to Infants
    Journal of aerosol medicine and pulmonary drug delivery, 2020
    Co-Authors: Connor Howe, Michael Hindle, Serena Bonasera, Vijaya Krishna Rani, P. Worth Longest
    Abstract:

    Background: Positive-pressure dry powder inhalers (DPIs) have recently been developed that in combination with highly dispersible spray-dried powder formulations can achieve high efficiency aerosolization with low actuation air-volumes (AAVs). The objective of this study was to initially develop the positive-pressure air-jet DPI platform for high efficiency aerosol delivery to newborn infants by using the nose-to-lung route. Methods: Aerosolization performance metrics of six air-jet DPIs were first assessed at AAVs that were consistent with full-term (30 mL) and preterm (10 mL) neonates. Designs of the air-jet DPIs varied based on geometry of the inlet and outlet flow passages and shape of the aerosolization chamber. Aerosolization metrics evaluated at the device outlet were emitted dose (ED) and mass median aerodynamic diameter (MMAD). Designs with the best aerosolization performance were connected to a smoothly expanding nasal interface and full-term infant (3550 g) nose-throat (NT) model with tracheal filter. Results: The three best performing devices had characteristics of a cylindrical and horizontal aerosolization chamber with a flush or protruding outlet orifice. Including multiple air inlets resulted in meeting the aerosolization targets of >80% ED (based on loaded dose) and MMAD

  • Devices for Improved Delivery of Nebulized Pharmaceutical Aerosols to the Lungs
    Journal of aerosol medicine and pulmonary drug delivery, 2019
    Co-Authors: Worth Longest, Benjamin M. Spence, Michael Hindle
    Abstract:

    Nebulizers have a number of advantages for the delivery of inhaled Pharmaceutical Aerosols, including the use of aqueous formulations and the ability to deliver process-sensitive proteins, peptides, and biological medications. A frequent disadvantage of nebulized Aerosols is poor lung delivery efficiency, which wastes valuable medications, increases delivery times, and may increase side effects of the medication. A focus of previous development efforts and previous nebulizer reviews, has been an improvement of the underlying nebulization technology controlling the breakup of a liquid into droplets. However, for a given nebulization technology, a wide range of secondary devices and strategies can be implemented to significantly improve lung delivery efficiency of the aerosol. This review focuses on secondary devices and technologies that can be implemented to improve the lung delivery efficiency of nebulized Aerosols and potentially target the region of drug delivery within the lungs. These secondary devices may (1) modify the aerosol size distribution, (2) synchronize aerosol delivery with inhalation, (3) reduce system depositional losses at connection points, (4) improve the patient interface, or (5) guide patient inhalation. The development of these devices and technologies is also discussed, which often includes the use of computational fluid dynamic simulations, three-dimensional printing and rapid prototype device and airway model construction, realistic in vitro experiments, and in vivo analysis. Of the devices reviewed, the implementation of streamlined components may be the most direct and lowest cost approach to enhance aerosol delivery efficiency within nonambulatory nebulizer systems. For applications involving high-dose medications or precise dose administration, the inclusion of active devices to control aerosol size, guide inhalation, and synchronize delivery with inhalation hold considerable promise.

  • Application of an inline dry powder inhaler to deliver high dose Pharmaceutical Aerosols during low flow nasal cannula therapy.
    International journal of pharmaceutics, 2018
    Co-Authors: Dale Farkas, Michael Hindle, P. Worth Longest
    Abstract:

    Abstract Inline dry powder inhalers (DPIs) offer a potentially effective option to deliver high dose inhaled medications simultaneously with mechanical ventilation. The objective of this study was to develop an inline DPI that is actuated using a low volume of air (LV-DPI) to efficiently deliver Pharmaceutical Aerosols during low flow nasal cannula (LFNC) therapy. A characteristic feature of the new inline LV-DPIs was the use of hollow capillary tubes that both pierced the capsule and provided a pathway for inlet air and exiting aerosol. Aerosolization characteristics, LFNC depositional losses and emitted dose (ED) were determined using 10 mg powder masses of a small-particle excipient enhanced growth (EEG) formulation. While increasing the number of inlet capillaries from one to three did not improve performance, retracting the inlet and outlet capillaries did improve ED by over 30%. It was theorized that high quality performance requires both high turbulent energy to deaggregate the powder and high wall shear stresses to minimize capsule retention. Best case performance included a device ED of approximately 85% (of loaded dose) and device emitted mass median aerodynamic diameter of 1.77 µm. Maximum ED through the LFNC system and small diameter (4 mm) nasal cannula was approximately 65% of the loaded dose. Potential applications of this device include the delivery of high dose inhaled medications such as surfactants, antibiotics, mucolytics, and anti-inflammatories.

  • In Vitro Assessment of Small Charged Pharmaceutical Aerosols in a Model of a Ventilated Neonate
    Journal of aerosol science, 2017
    Co-Authors: Landon Holbrook, Michael Hindle, P. Worth Longest
    Abstract:

    Aerosolized medications may benefit infants receiving mechanical ventilation; however, the lung delivery efficiency of these Aerosols is unacceptably low. In vitro experiments were conducted to evaluate aerosol delivery through conventional and modified ventilation systems to the end of a 3mm endotracheal tube (ETT) under steady state and realistic cyclic flow conditions. System modifications were employed to investigate the use of small charged particles and included streamlined components, a reduction in nebulizer liquid flow rate, synchronization with inspiration, and implementation of a previously designed low-flow induction charger (LF-IC), which was further modified in this study. Cyclic flow experiments implemented a modern ventilator with bias airflow and an inline flow meter, both of which are frequently excluded from in vitro tests but included in clinical practice. The modified LF-IC system demonstrated superior delivery efficiency to the end of the ETT (34%) compared with the commercial system (~1.3%) operating under cyclic ventilation conditions. These findings indicate that commercial systems still provide very low lung delivery efficiencies despite decades of innovation. In contrast, the modified system increased dose delivery to the end of the ETT by 26-fold. Despite initial concerns, the charged aerosol could be efficiently delivered through the small diameter ETT and reach the lungs. Future studies will be required to determine if the applied particle charge can eliminate expected high exhalation aerosol loss and will require the development of a realistic lung model.

Warren H Finlay - One of the best experts on this subject based on the ideXlab platform.

  • An Exploration of Factors Affecting In Vitro Deposition of Pharmaceutical Aerosols in the Alberta Idealized Throat.
    Journal of aerosol medicine and pulmonary drug delivery, 2019
    Co-Authors: Conor A. Ruzycki, Andrew R. Martin, Warren H Finlay
    Abstract:

    Abstract Background: The development of accurate in vitro—in vivo correlations requires the consideration of a number of factors in vitro, including the emulation of upper airway geometry, inhalati...

  • Improved prediction of intersubject variability in extrathoracic aerosol deposition using algebraic correlations
    Aerosol Science and Technology, 2017
    Co-Authors: Conor A. Ruzycki, Hak-kim Chan, Michael Yang, Warren H Finlay
    Abstract:

    For inhaled Pharmaceutical Aerosols, large in vivo intersubject variability in respiratory tract deposition (Heyder et al. 1982; Rudolf et al. 1994) can confound a priori prediction of device perfo...

  • in vivo in vitro correlations predicting pulmonary drug deposition from Pharmaceutical Aerosols
    Journal of Aerosol Medicine and Pulmonary Drug Delivery, 2010
    Co-Authors: Peter R. Byron, Michael Hindle, Worth P Longest, Carlos F. Lange, Donald Mcrobbie, Michael J. Oldham, Bo Olsson, Charles G. Thiel, Herbert Wachtel, Warren H Finlay
    Abstract:

    Abstract In order to answer the question “what research remains to be done?” we review the current state of the art in Pharmaceutical aerosol deposition modeling and explore possible in vivo– in vitro correlations (IVIVC) linking drug deposition in the human lung to predictions made using in vitro physical airway models and in silico computer models. The use of physical replicas of portions of the respiratory tract is considered, alongside the advantages and disadvantages of the different imaging methods used to obtain their dimensions. The use of airway replicas to determine drug deposition in vitro is discussed and compared with the predictions from different empirical curve fits to long-standing in vivo deposition data for monodisperse Aerosols. The use of improved computational models and three-dimensional computational fluid dynamics (CFD) to predict aerosol deposition within the respiratory tract is examined. CFD's ability to predict both drug deposition from Pharmaceutical aerosol sprays and powder...

  • In Vivo–In Vitro Correlations: Predicting Pulmonary Drug Deposition from Pharmaceutical Aerosols
    Journal of Aerosol Medicine and Pulmonary Drug Delivery, 2010
    Co-Authors: Peter R. Byron, P. Worth Longest, Michael Hindle, Carlos F. Lange, Donald Mcrobbie, Michael J. Oldham, Bo Olsson, Charles G. Thiel, Herbert Wachtel, Warren H Finlay
    Abstract:

    Abstract In order to answer the question “what research remains to be done?” we review the current state of the art in Pharmaceutical aerosol deposition modeling and explore possible in vivo– in vitro correlations (IVIVC) linking drug deposition in the human lung to predictions made using in vitro physical airway models and in silico computer models. The use of physical replicas of portions of the respiratory tract is considered, alongside the advantages and disadvantages of the different imaging methods used to obtain their dimensions. The use of airway replicas to determine drug deposition in vitro is discussed and compared with the predictions from different empirical curve fits to long-standing in vivo deposition data for monodisperse Aerosols. The use of improved computational models and three-dimensional computational fluid dynamics (CFD) to predict aerosol deposition within the respiratory tract is examined. CFD's ability to predict both drug deposition from Pharmaceutical aerosol sprays and powder...

  • In vivo-in vitro correlations: predicting pulmonary drug deposition from Pharmaceutical Aerosols.
    Journal of aerosol medicine and pulmonary drug delivery, 2010
    Co-Authors: Peter R. Byron, P. Worth Longest, Michael Hindle, Carlos F. Lange, Donald Mcrobbie, Michael J. Oldham, Bo Olsson, Charles G. Thiel, Herbert Wachtel, Warren H Finlay
    Abstract:

    In order to answer the question "what research remains to be done?" we review the current state of the art in Pharmaceutical aerosol deposition modeling and explore possible in vivo- in vitro correlations (IVIVC) linking drug deposition in the human lung to predictions made using in vitro physical airway models and in silico computer models. The use of physical replicas of portions of the respiratory tract is considered, alongside the advantages and disadvantages of the different imaging methods used to obtain their dimensions. The use of airway replicas to determine drug deposition in vitro is discussed and compared with the predictions from different empirical curve fits to long-standing in vivo deposition data for monodisperse Aerosols. The use of improved computational models and three-dimensional computational fluid dynamics (CFD) to predict aerosol deposition within the respiratory tract is examined. CFD's ability to predict both drug deposition from Pharmaceutical aerosol sprays and powder behavior in dry powder inhalers is examined; both were highlighted as important areas for future research. Although the authors note the abilities of current in vitro and in silico methods to predict in vivo data, a number of limitations remain. These include our present inability to either image or replicate all but the most proximal airways in sufficient spatial and temporal detail to allow full capture of the fluid and aerosol mechanics in these regions. In addition, the highly complex microscale behavior of Aerosols within inhalers and the respiratory tract places extreme computational demands on in silico methods. When the complexity of variations in respiratory tract geometry is associated with additional factors such as breathing pattern, age, disease state, postural position, and patient-device interaction are all considered, it is clear that further research is required before the prediction of all aspects of inhaled Pharmaceutical aerosol deposition is possible.

Geng Tian - One of the best experts on this subject based on the ideXlab platform.

  • Pharmaceutical Aerosols deposition patterns from a dry powder inhaler euler lagrangian prediction and validation
    Medical Engineering & Physics, 2017
    Co-Authors: R Kannan, Geng Tian, Renishkumar Delvadia, Narender Singh, Andrzej Przekwas, Ross Walenga
    Abstract:

    Abstract This study uses Computational Fluid Dynamics (CFD) to predict, analyze and validate the deposition patterns in a human lung for a Budesonide drug delivered from the Novolizer Dry Powder Inhaler device. We used a test case of known deposition patterns to validate our computational Euler Lagrangian-based deposition predictions. Two different lung models are used: (i) a basic ring-less trachea model and (ii) an advanced Human Zygote5 model. Unlike earlier attempts, the current simulations do not include the device in the computational domain. This greatly reduces the computational effort. To mimic the device, we model the inlet particle jet stream from the device as a spray entering the mouth in a conical fashion. Deposition studies in the various lung regions were performed. We were able to computationally predict and then demonstrate the enhanced deposition in the tracheal and first generation rings/ridges. The enhanced vorticity creation due to the ring structure and the geometrical design contributes to larger deposition in the Zygote5 model. These are in accord with existing data, unlike the ring-less model. Our validated results indicate the need to (i) introduce the ridges in the experimental casts and the CFD surface meshes to be anatomically consistent and obtain physiologically consistent depositions; (ii) introduce a factor to account for the recirculating lighter particles in empirical models.

  • Validating CFD Predictions of Pharmaceutical Aerosol Deposition with In Vivo Data
    Pharmaceutical Research, 2015
    Co-Authors: Geng Tian, Michael Hindle, Sau Lee, P. Worth Longest
    Abstract:

    Purpose CFD provides a powerful approach to evaluate the deposition of Pharmaceutical Aerosols; however, previous studies have not compared CFD results of deposition throughout the lungs with in vivo data. Methods The in vivo datasets selected for comparison with CFD predictions included fast and slow clearance of monodisperse Aerosols as well as 2D gamma scintigraphy measurements for a dry powder inhaler (DPI) and softmist inhaler (SMI). The CFD model included the inhaler, a characteristic model of the mouth-throat (MT) and upper tracheobronchial (TB) airways, stochastic individual pathways (SIPs) representing the remaining TB region, and recent CFD-based correlations to predict Pharmaceutical aerosol deposition in the alveolar airways. Results For the monodisperse aerosol, CFD predictions of total lung deposition agreed with in vivo data providing a percent relative error of 6% averaged across aerosol sizes of 1–7 μm. With the DPI and SMI, deposition was evaluated in the MT, central airways (bifurcations B1-B7), and intermediate plus peripheral airways (B8 through alveoli). Across these regions, CFD predictions produced an average relative error

  • Validating CFD Predictions of Pharmaceutical Aerosol Deposition with In Vivo Data
    Pharmaceutical research, 2015
    Co-Authors: Geng Tian, Michael Hindle, Sau L. Lee, P. Worth Longest
    Abstract:

    Purpose CFD provides a powerful approach to evaluate the deposition of Pharmaceutical Aerosols; however, previous studies have not compared CFD results of deposition throughout the lungs with in vivo data.

  • Performance of Combination Drug and Hygroscopic Excipient Submicrometer Particles from a Softmist Inhaler in a Characteristic Model of the Airways
    Annals of Biomedical Engineering, 2012
    Co-Authors: P. Worth Longest, Geng Tian, Yoen-ju Son, Michael Hindle
    Abstract:

    Excipient enhanced growth (EEG) of inhaled submicrometer Pharmaceutical Aerosols is a recently proposed method intended to significantly reduce extrathoracic deposition and improve lung delivery. The objective of this study was to evaluate the size increase of combination drug and hygroscopic excipient particles in a characteristic model of the airways during inhalation using both in vitro experiments and computational fluid dynamic (CFD) simulations. The airway model included a characteristic mouth-throat (MT) and upper tracheobronchial (TB) region through the third bifurcation and was enclosed in a chamber geometry used to simulate the thermodynamic conditions of the lungs. Both in vitro results and CFD simulations were in close agreement and indicated that EEG delivery of combination submicrometer particles could nearly eliminate MT deposition for inhaled Pharmaceutical Aerosols. Compared with current inhalers, the proposed delivery approach represents a 1–2 order of magnitude reduction in MT deposition. Transient inhalation was found to influence the final size of the aerosol based on changes in residence times and relative humidity values. Aerosol sizes following EEG when exiting the chamber (2.75–4.61  μ m) for all cases of initial submicrometer combination particles were equivalent to or larger than many conventional Pharmaceutical Aerosols that frequently have MMADs in the range of 2–3  μ m.

  • Comparing MDI and DPI Aerosol Deposition Using In Vitro Experiments and a New Stochastic Individual Path (SIP) Model of the Conducting Airways
    Pharmaceutical Research, 2012
    Co-Authors: P. Worth Longest, Geng Tian, Ross L. Walenga, Michael Hindle
    Abstract:

    Purpose Deposition characteristics of MDI and DPI Aerosols were compared throughout the conducting airways for the first time using a combination of in vitro experiments and a newly developed stochastic individual path (SIP) model for different inhalation profiles. Methods In vitro experiments were used to determine initial particle distribution profiles and to validate computational fluid dynamics (CFD) model results for a MDI and DPI delivering the same dose of drug in a geometry of the mouth-throat and tracheobronchial airways. The validated CFD model was then used to predict the transport and deposition of the drug using correct and incorrect inhalation profiles for each inhaler. Results The MDI delivered approximately two times more drug to the tracheobronchial region compared with the DPI for both correct and incorrect inhalation profiles. Errors in inhalation reduced the deposited tracheobronchial dose by approximately 30% for both inhalers. The DPI delivered the largest dose to the mouth-throat (~70%) and the MDI delivered the largest dose to the alveolar airways (~50%). Conclusions The developed in silico model provides new insights into the lung delivery of Pharmaceutical Aerosols and can be applied in future studies in combination with pharmacokinetic analysis to establish bioequivalence between devices.

Peter R. Byron - One of the best experts on this subject based on the ideXlab platform.

  • in vivo in vitro correlations predicting pulmonary drug deposition from Pharmaceutical Aerosols
    Journal of Aerosol Medicine and Pulmonary Drug Delivery, 2010
    Co-Authors: Peter R. Byron, Michael Hindle, Worth P Longest, Carlos F. Lange, Donald Mcrobbie, Michael J. Oldham, Bo Olsson, Charles G. Thiel, Herbert Wachtel, Warren H Finlay
    Abstract:

    Abstract In order to answer the question “what research remains to be done?” we review the current state of the art in Pharmaceutical aerosol deposition modeling and explore possible in vivo– in vitro correlations (IVIVC) linking drug deposition in the human lung to predictions made using in vitro physical airway models and in silico computer models. The use of physical replicas of portions of the respiratory tract is considered, alongside the advantages and disadvantages of the different imaging methods used to obtain their dimensions. The use of airway replicas to determine drug deposition in vitro is discussed and compared with the predictions from different empirical curve fits to long-standing in vivo deposition data for monodisperse Aerosols. The use of improved computational models and three-dimensional computational fluid dynamics (CFD) to predict aerosol deposition within the respiratory tract is examined. CFD's ability to predict both drug deposition from Pharmaceutical aerosol sprays and powder...

  • In Vivo–In Vitro Correlations: Predicting Pulmonary Drug Deposition from Pharmaceutical Aerosols
    Journal of Aerosol Medicine and Pulmonary Drug Delivery, 2010
    Co-Authors: Peter R. Byron, P. Worth Longest, Michael Hindle, Carlos F. Lange, Donald Mcrobbie, Michael J. Oldham, Bo Olsson, Charles G. Thiel, Herbert Wachtel, Warren H Finlay
    Abstract:

    Abstract In order to answer the question “what research remains to be done?” we review the current state of the art in Pharmaceutical aerosol deposition modeling and explore possible in vivo– in vitro correlations (IVIVC) linking drug deposition in the human lung to predictions made using in vitro physical airway models and in silico computer models. The use of physical replicas of portions of the respiratory tract is considered, alongside the advantages and disadvantages of the different imaging methods used to obtain their dimensions. The use of airway replicas to determine drug deposition in vitro is discussed and compared with the predictions from different empirical curve fits to long-standing in vivo deposition data for monodisperse Aerosols. The use of improved computational models and three-dimensional computational fluid dynamics (CFD) to predict aerosol deposition within the respiratory tract is examined. CFD's ability to predict both drug deposition from Pharmaceutical aerosol sprays and powder...

  • In vivo-in vitro correlations: predicting pulmonary drug deposition from Pharmaceutical Aerosols.
    Journal of aerosol medicine and pulmonary drug delivery, 2010
    Co-Authors: Peter R. Byron, P. Worth Longest, Michael Hindle, Carlos F. Lange, Donald Mcrobbie, Michael J. Oldham, Bo Olsson, Charles G. Thiel, Herbert Wachtel, Warren H Finlay
    Abstract:

    In order to answer the question "what research remains to be done?" we review the current state of the art in Pharmaceutical aerosol deposition modeling and explore possible in vivo- in vitro correlations (IVIVC) linking drug deposition in the human lung to predictions made using in vitro physical airway models and in silico computer models. The use of physical replicas of portions of the respiratory tract is considered, alongside the advantages and disadvantages of the different imaging methods used to obtain their dimensions. The use of airway replicas to determine drug deposition in vitro is discussed and compared with the predictions from different empirical curve fits to long-standing in vivo deposition data for monodisperse Aerosols. The use of improved computational models and three-dimensional computational fluid dynamics (CFD) to predict aerosol deposition within the respiratory tract is examined. CFD's ability to predict both drug deposition from Pharmaceutical aerosol sprays and powder behavior in dry powder inhalers is examined; both were highlighted as important areas for future research. Although the authors note the abilities of current in vitro and in silico methods to predict in vivo data, a number of limitations remain. These include our present inability to either image or replicate all but the most proximal airways in sufficient spatial and temporal detail to allow full capture of the fluid and aerosol mechanics in these regions. In addition, the highly complex microscale behavior of Aerosols within inhalers and the respiratory tract places extreme computational demands on in silico methods. When the complexity of variations in respiratory tract geometry is associated with additional factors such as breathing pattern, age, disease state, postural position, and patient-device interaction are all considered, it is clear that further research is required before the prediction of all aspects of inhaled Pharmaceutical aerosol deposition is possible.

  • Calibration of the Modified Electrical Low-Pressure Impactor (ELPI) for Use with Pressurized Pharmaceutical Aerosols
    Journal of aerosol medicine and pulmonary drug delivery, 2009
    Co-Authors: Reshma Kotian, Joanne Peart, Joan Bryner, Peter R. Byron
    Abstract:

    The modified Electrical Low Pressure Impactor (ELPI) is currently being used in several laboratories to determine inherent electrostatic charge of Pharmaceutical Aerosols as a function of their particle size. However, the ELPI appears to underestimate the aerodynamic particle size distributions (aPSDs) of pressurized metered dose inhalers (pMDIs), casting doubt upon the manufacturer's calibration. In the present study, four commercially available pMDIs with a range of aPSDs were used to recalibrate cutoff diameters (d50s) of the ELPI stages using a reference ACI. Particle size analyses were performed in a mensurated ACI and a calibrated modified ELPI (n = 5); stage coating was employed in both instruments. The ACI data were fitted to a lognormal cumulative distribution function by nonlinear regression analysis. Best estimates for mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) for each pMDI were obtained and used in combination with impaction results from the modified ELPI t...

  • product quality research institute evaluation of cascade impactor profiles of Pharmaceutical Aerosols part 3 final report on a statistical procedure for determining equivalence
    Aaps Pharmscitech, 2007
    Co-Authors: David Christopher, Craig A Dunbar, Peter R. Byron, Wallace P Adams, Svetlana Lyapustina, Anthony Amann, Craig M Bertha, William H Doub, Walter W Hauck, Jolyon P Mitchell
    Abstract:

    The purpose of this article is to report final results of the evaluation of a chi-square ratio test proposed by the US Food and Drug Administration (FDA) for demonstrating equivalence of aerodynamic particle size distribution (APSD) profiles of nasal and orally inhaled drug products. A working group of the Product Quality Research Institute previously published results demonstrating some limitations of the proposed test. In an effort to overcome the test’s limited discrimination, the group proposed a supplemental test, a population bioequivalence (PBE) test for impactor-sized mass (ISM). In this final report the group compares the chi-square ratio test to the ISM-PBE test and to the combination of both tests. The basis for comparison is a set of 55 realistic scenarios of cascade impactor data, which were evaluated for equivalence by the statistical tests and independently by the group members. In many instances, the combined application of these 2 tests appeared to increase the discriminating ability of the statistical procedure compared with the chi-square ratio test alone. In certain situations the chi-square ratio test alone was sufficient to determine equivalence of APSD profiles, while in other situations neither of the tests alone nor their combination was adequate. This report describes all of these scenarios and results. In the end, the group did not recommend a statistical test for APSD profile equivalence. The group did not investigate other in vitro tests, in vivo issues, or other statistical tests for APSD profile comparisons. The studied tests are not intended for routine quality control of APSD.