Challenges in inhaled product development and opportunities for open innovation

Forbes, Ben; Asgharian, Bahman; Dailey, Lea Ann; Ferguson, Douglas; Gerde, Per; Gumbleton, Mark; Gustavsson, Lena; Hardy, Colin; Hassall, David G.; Jones, Rhys; Lock, Ruth; Maas, Janet; McGovern, Tim; Pitcairn, Gary R.; Somers, Graham; Wolff, Ron

doi:10.1016/j.addr.2010.11.004

Cited by 105 publications

(65 citation statements)

References 161 publications

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“…Indeed pharmacokinetic publications on inhaled drugs tend to focus on plasma or blood pharmacokinetics and/or pharmacodynamic responses rather than what is actually happening to the drug in the target organ [10,11,12]. In particular there is limited published understanding of how drug properties can influence lung pharmacokinetics and the impact these may have on its therapeutic potential [13]. This situation may be linked to the difficulty of producing and interpreting lung concentration data across relevant species.…”

Section: Introductionmentioning

confidence: 99%

Optimisation of DMPK by the Inhaled Route: Challenges and Approaches

Cooper¹,

Ferguson²,

Grime³

2012

CDM

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The renewed interest in inhalation delivery over recent years has led to an expansion in the understanding of lung pharmacokinetics. Historically optimisation of inhaled drugs focused largely on development of material properties, consistent with achieving a good lung deposition, alongside demonstrating appropriate in vivo efficacy with little understanding of the relationship to pharmacokinetics in the lung. Recent efforts have led to an increased understanding of lung concentrations and how to maximise exposure in order to achieve the desired pharmacological response at a dose consistent with development of an inhaled product. Although there is a prerequisite for excellent potency in inhalation delivery, it is essential that this be combined with pharmacokinetic properties that allow sufficient free concentration at the effect site in lung to exert the pharmacological response for an appropriate dosing interval. Increases in basicity, polarity and/or decreases in aqueous solubility can extend pharmacokinetic duration and assist in finding the right balance between lung and systemic exposure. Current evidence suggests there are similarities in lung retention in rat and dog and that animal lung concentration data can enable pharmacokinetic-pharmacodynamic relationships to be derived thus providing more confidence in the requirements for man. Although inhaled delivery is challenging from a pharmacokinetic point of view, direct evaluation of exposure in the target organ has enabled further understanding of the drivers for drug disposition and highlighted the need for further development of predictive lung pharmacokinetic tools in the future.

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Section: Introductionmentioning

confidence: 99%

Optimisation of DMPK by the Inhaled Route: Challenges and Approaches

Cooper¹,

Ferguson²,

Grime³

2012

CDM

Self Cite

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“…Especially the CVD process facilitates an adequate polymer deposition on basic aperture plates in order to achieve the desired final aerosol droplet size. Thus, this coating technique allows easy prototyping and optimization of nebulizer characteristics, which could be of significant benefit for personalized medicine applications (Denyer et al 2004;Watts et al 2008;Forbes et al 2011), where the aerosol properties could be tailored to match the needs of the individual patient population. Naturally, the described approach is not limited to the field of inhalative therapy; it may also be applied to a variety of other liquid atomization processes (e.g., spray drying, mass spectroscopy or ink-jet printing), during emulsion or foam formation and furthermore, for filtration and patch clamp purposes.…”

Section: Discussionmentioning

confidence: 99%

Customized Vibrating-Membrane Nozzles for Enhanced Fluid Atomization

Beck-Broichsitter

Schmehl

Seeger

2015

Aerosol Science and Technology

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“…Over the last few decades, inhaled product development has seen huge success with hundreds of medications making it to the market (Forbes et al, 2011). Medications providing relief to local lung diseases such as asthma and (Kleinstreuer, Zhang and Donohue, 2008;Kunda et al, 2013)) chronic obstructive pulmonary disorder (COPD) are the major drivers for the inhalation market (Hickey, 2013).…”

Section: Pulmonary Drug Delivery Marketmentioning

confidence: 99%

Challenges Associated with the Pulmonary Delivery of Therapeutic Dry Powders for Preclinical Testing

Price

Kunda

Muttil

2019

KONA

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Significant progress has been made over the last half-century in delivering therapeutics by the pulmonary route. Inhaled therapeutics are administered to humans using metered-dose inhalers, nebulizers, or dry powder inhalers, and each device requires a different formulation strategy for the therapeutic to be successfully delivered into the lung. In recent years, there has been a shift to the use of dry powder inhalers due to advantages in the consistency of the dose delivered, ease of administration, and formulation stability. Numerous preclinical studies, involving small and large animals, have evaluated dry powder drugs, vaccines, and immunotherapeutics delivered by the pulmonary route. These studies used different dry powder delivery devices including nose-only, whole-body, and intratracheal administration systems, each of which works with different aerosolization mechanisms. Unfortunately, these delivery platforms usually lead to variable powder deposition in the respiratory tract of animals. In this review, we will discuss obstacles and variables that affect successful pulmonary delivery and uniform powder deposition in the respiratory tract, such as the type of delivery device, dry powder formulation, and the animal model used. We will conclude by outlining factors that enhance the reproducible deposition of dry powders in the respiratory tract of preclinical animal models and identifying knowledge and technology gaps within the field. We will also outline the important factors necessary for successful translation of studies performed in preclinical models to humans.

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Challenges in inhaled product development and opportunities for open innovation

Cited by 105 publications

References 161 publications

Optimisation of DMPK by the Inhaled Route: Challenges and Approaches

Optimisation of DMPK by the Inhaled Route: Challenges and Approaches

Customized Vibrating-Membrane Nozzles for Enhanced Fluid Atomization

Challenges Associated with the Pulmonary Delivery of Therapeutic Dry Powders for Preclinical Testing

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