Degree of Throat Deposition Can Explain the Variability in Lung Deposition of Inhaled Drugs

Borgström, Lars; Olsson, Bo; Thorsson, Lars

doi:10.1089/jam.2006.19.473

Cited by 157 publications

(83 citation statements)

References 14 publications

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“…Oropharyngeal losses also vary with the inhalation maneuver through the same inhaler. The variability and uncertainty of lung deposition are mostly the result of variations in extrathoracic deposition, and it has been hypothesized that throat deposition is the major determinant for lung deposition of inhaled aerosols [124]. It may be clear that what is 'lost' in the mouth-throat region does not contribute to the therapeutic effect and can cause adverse local (or systemic) side effects.…”

Section: Dpi Design and Pulmonary Drug Deposition And Distributionmentioning

confidence: 99%

Dry powder inhalation: past, present and future

Boer

Hagedoorn

Hoppentocht

et al. 2016

Expert Opinion on Drug Delivery

221

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Introduction: Early dry powder inhalers (DPIs) were designed for low drug doses in asthma and COPD therapy. Nearly all concepts contained carrier-based formulations and lacked efficient dispersion principles. Therefore, particle engineering and powder processing are increasingly applied to achieve acceptable lung deposition with these poorly designed inhalers. Areas covered: The consequences of the choices made for early DPI development with respect of efficacy, production costs and safety and the tremendous amount of energy put into understanding and controlling the dispersion performance of adhesive mixtures are discussed. Also newly developed particle manufacturing and powder formulation processes are presented as well as the challenges, objectives, and new tools available for future DPI design. Expert opinion: Improved inhaler design is desired to make DPIs for future applications cost-effective and safe. With an increasing interest in high dose drug delivery, vaccination and systemic delivery via the lungs, innovative formulation technologies alone may not be sufficient. Safety is served by increasing patient adherence to the therapy, minimizing the use of unnecessary excipients and designing simple and self-intuitive inhalers, which give good feedback to the patient about the inhalation maneuver. For some applications, like vaccination and delivery of hygroscopic formulations, disposable inhalers may be preferred. ARTICLE HISTORY

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Section: Dpi Design and Pulmonary Drug Deposition And Distributionmentioning

confidence: 99%

Dry powder inhalation: past, present and future

Boer

Hagedoorn

Hoppentocht

et al. 2016

Expert Opinion on Drug Delivery

221

View full text Add to dashboard Cite

show abstract

“…Theoretically, reduced extrathoracic deposition associated with ECG delivery should largely decrease variability in deposition associated with the geometry. (31) However, further studies are needed in patient specific extrathoracic models developed from individuals to assess the effects of the current approximate model, intersubject variability, and to extend the ECG delivery approach to children and infants. Furthermore, the airflow through commercially available nasal cannula may introduce flow field artifacts that are different from the simple models considered in this study.…”

Section: Discussionmentioning

confidence: 99%

“…A recent review of orally inhaled products by Borgstrom et al (31) indicated that high drug losses in the inhaler and extrathoracic airways correlated directly with high variability in lung delivery. It is reasonable that high delivery system and nasal losses during NIV will also produce high variability in the amount of drug aerosol reaching the lungs.…”

Section: Introductionmentioning

confidence: 99%

Improving the Lung Delivery of Nasally Administered Aerosols During Noninvasive Ventilation—An Application of Enhanced Condensational Growth (ECG)

Longest

Tian²,

Hindle³

2011

Journal of Aerosol Medicine and Pulmonary Drug Delivery

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Background: Aerosol drug delivery during noninvasive ventilation (NIV) is known to be inefficient due to high depositional losses. To improve drug delivery efficiency, the concept of enhanced condensational growth (ECG) was recently proposed in which a submicrometer or nanoaerosol reduces extrathoracic deposition and subsequent droplet size increase promotes lung retention. The objective of this study was to provide proof-of-concept that the ECG approach could improve lung delivery of nasally administered aerosols under conditions consistent with NIV. Methods: Aerosol deposition and size increase were evaluated in an adult nose-mouth-throat (NMT) replica geometry using both in vitro experiments and CFD simulations. For the ECG delivery approach, separate streams of a submicrometer aerosol and warm (398C) saturated air were generated and delivered to the right and left nostril inlets, respectively. A control case was also considered in which an aerosol with a mass median aerodynamic diameter (MMAD) of 4.67 mm was delivered to the model. Results: In vitro experiments showed that the ECG approach significantly reduced the drug deposition fraction in the NMT geometry compared with the control case [14.8 (1.83)%-ECG vs. 72.6 (3.7)%-control]. Aerosol size increased from an initial MMAD of 900 nm to a size of approximately 2 mm at the exit of the NMT geometry.Results of the CFD model were generally in good agreement with the experimental findings. Based on CFD predictions, increasing the delivery temperature of the aerosol stream from 21 to 358C under ECG conditions further reduced the total NMT drug deposition to 5% and maintained aerosol growth by ECG to approximately 2 mm. Conclusions: Application of the ECG approach may significantly improve the delivery of pharmaceutical aerosols during NIV and may open the door for using the nasal route to routinely deliver pulmonary medications.

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“…However, a literature survey demonstrated that the throat plays an important role in determining lung deposition of inhaled particles and that the inconsistency observed in lung deposition is often due to the inconsistency occurring in the throat deposition (14). To evaluate the effects of upper airway on the lungs, a realistic human upper airway model was simulated by a computational method and compared with results obtained in an airway model starting from the trachea (95).…”

Section: In Silico Lung Modelingmentioning

confidence: 99%

Computational and bioengineered lungs as alternatives to whole animal, isolated organ, and cell-based lung models

Patel

Gauvin

Absar

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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Development of lung models for testing a drug substance or delivery system has been an intensive area of research. However, a model that mimics physiological and anatomical features of human lungs is yet to be established. Although in vitro lung models, developed and fine-tuned over the past few decades, were instrumental for the development of many commercially available drugs, they are suboptimal in reproducing the physiological microenvironment and complex anatomy of human lungs. Similarly, intersubject variability and high costs have been major limitations of using animals in the development and discovery of drugs used in the treatment of respiratory disorders. To address the complexity and limitations associated with in vivo and in vitro models, attempts have been made to develop in silico and tissue-engineered lung models that allow incorporation of various mechanical and biological factors that are otherwise difficult to reproduce in conventional cell or organ-based systems. The in silico models utilize the information obtained from in vitro and in vivo models and apply computational algorithms to incorporate multiple physiological parameters that can affect drug deposition, distribution, and disposition upon administration via the lungs. Bioengineered lungs, on the other hand, exhibit significant promise due to recent advances in stem or progenitor cell technologies. However, bioengineered approaches have met with limited success in terms of development of various components of the human respiratory system. In this review, we summarize the approaches used and advancements made toward the development of in silico and tissue-engineered lung models and discuss potential challenges associated with the development and efficacy of these models. bioengineered lung; computational modeling; in silico; lung models; tissue engineering LUNG DISEASES ARE THE THIRD leading cause of deaths in the United States that translate into one in six deaths. More than 400,000 Americans die of lung disease every year and around 35 million are now living with chronic lung problems (1). Therefore, there is an important need to understand as to how a new drug entity or a novel formulation may influence the anatomy, physiology, and pathogenesis of lungs and vice versa.The human lung has an approximate volume of six liters, contains about 300 million alveoli, and provides a total surface area of 100 square meters as blood-air interface, which is packed into an elastic dynamic structure responsible for gas exchange (159). The human airway wall is a connective tissue that includes smooth muscle cells (SMC), mucus glands, blood vessels, and fibroblasts surrounded by a collagen-rich extracellular matrix (ECM). Epithelial cells, responsible for the efficient oxygen and carbon dioxide transfer, are at the interface between air and the connective tissue and are attached to an underlying basement membrane. The respiratory system is the site of a variety of pulmonary diseases such as asthma, bronchitis, pneumonia, cystic fibrosis, emphysema, a...

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Degree of Throat Deposition Can Explain the Variability in Lung Deposition of Inhaled Drugs

Cited by 157 publications

References 14 publications

Dry powder inhalation: past, present and future

Dry powder inhalation: past, present and future

Improving the Lung Delivery of Nasally Administered Aerosols During Noninvasive Ventilation—An Application of Enhanced Condensational Growth (ECG)

Computational and bioengineered lungs as alternatives to whole animal, isolated organ, and cell-based lung models

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