Advances in Inhaled Technologies: Understanding the Therapeutic Challenge, Predicting Clinical Performance, and Designing the Optimal Inhaled Product

Bäckman, Per; Adelmann, Holger G.; Petersson, Gunilla; Jones, Chris

doi:10.1038/clpt.2014.27

Cited by 55 publications

(38 citation statements)

References 55 publications

(74 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For slowly dissolving compounds, therapeutic effect is sensitive to material properties governing solubility and/or dissolution rate. This has been demonstrated experimentally: a difference in systemic exposure between two formulations with similar aerodynamic particle size distributions was consistent with predicted difference in the dissolution rate (21). A relationship between dissolution rate and appearance of drug in plasma has also been reported (35).…”

Section: Dissolution Permeation Particle Clearance and Tissue Exposupporting

confidence: 76%

“…Common means of retaining inhaled drugs in the lungs include tissue entrapment (e.g., water soluble di-bases) and slow dissolution of particles of poorly soluble drugs such as corticosteroids ( Fig. 2) (21). For compounds with high water solubility such as the di-bases, sustained local tissue concentration, and hence therapeutic effect, is influenced mainly by the extent of tissue binding or tissue entrapment which is governed by molecular properties rather than material or formulation properties.…”

Section: Dissolution Permeation Particle Clearance and Tissue Expomentioning

confidence: 99%

See 1 more Smart Citation

In Vitro Testing for Orally Inhaled Products: Developments in Science-Based Regulatory Approaches

Forbes

Bäckman

Christopher

et al. 2015

AAPS J

View full text Add to dashboard Cite

Abstract. This article is part of a series of reports from the "Orlando Inhalation Conference-Approaches in International Regulation" which was held in March 2014, and coorganized by the University of Florida and the International Pharmaceutical Aerosol Consortium on Regulation and Science (IPAC-RS). The goal of the conference was to foster the exchange of ideas and knowledge across the global scientific and regulatory community in order to identify and help move towards strategies for internationally harmonized, science-based regulatory approaches for the development and marketing approval of inhalation medicines, including innovator and second entry products. This article provides an integrated perspective of case studies and discussion related to in vitro testing of orally inhaled products, including in vitro-in vivo correlations and requirements for in vitro data and statistical analysis that support quality or bioequivalence for regulatory applications.

show abstract

Section: Dissolution Permeation Particle Clearance and Tissue Exposupporting

confidence: 76%

Section: Dissolution Permeation Particle Clearance and Tissue Expomentioning

confidence: 99%

In Vitro Testing for Orally Inhaled Products: Developments in Science-Based Regulatory Approaches

Forbes

Bäckman

Christopher

et al. 2015

AAPS J

View full text Add to dashboard Cite

show abstract

“…The rate and extent of absorption of inhaled drugs are determined by the relative rates of the different clearance mechanisms that operate in the lungs [1–3]. Clearance by absorptive transfer from the lung lumen is predominately controlled by the epithelial permeability of free (unbound) drug.…”

Section: Introductionmentioning

confidence: 99%

A Comparison of Drug Transport in Pulmonary Absorption Models: Isolated Perfused rat Lungs, Respiratory Epithelial Cell Lines and Primary Cell Culture

et al. 2017

View full text Add to dashboard Cite

PurposeTo evaluate the ability of human airway epithelial cell layers and a simple rat isolated perfused lung (IPL) model to predict pulmonary drug absorption in rats in vivo.MethodThe permeability of seven compounds selected to possess a range of lipophilicity was measured in two airway cell lines (Calu-3 and 16HBE14o-), in normal human bronchial epithelial (NHBE) cells and using a simple isolated perfused lungs (IPL) technique. Data from the cell layers and ex vivo lungs were compared to published absorption rates from rat lungs measured in vivo.ResultsA strong relationship was observed between the logarithm of the in vivo absorption half-life and the absorption half-life in the IPL (r = 0.97; excluding formoterol). Good log-linear relationships were also found between the apparent first-order absorption rate in vivo and cell layer permeability with correlation coefficients of 0.92, 0.93, 0.91 in Calu-3, 16HBE14o- and NHBE cells, respectively.ConclusionThe simple IPL technique provided a good prediction of drug absorption from the lungs, making it a useful method for empirical screening of drug absorption in the lungs. Permeability measurements were similar in all the respiratory epithelial cell models evaluated, with Calu-3 having the advantage for routine permeability screening purposes of being readily availability, robust and easy to culture.

show abstract

“…The compatibility between the inhalation device and the formulation, comprised of the active pharmaceutical ingredient (API) and the excipients, is essential to efficiently deliver the API to the target site. An ideal inhalation product must be easily operated, uncomplicated, handy, should deliver reproducible doses irrespective of temperature, humidity, and patient inspiratory flow rate (Bäckman et al, 2014). …”

Section: Formulation and Delivery Of Inhalation Productsmentioning

confidence: 99%

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

Price

Kunda

Muttil

2019

KONA

View full text Add to dashboard Cite

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.

show abstract

Advances in Inhaled Technologies: Understanding the Therapeutic Challenge, Predicting Clinical Performance, and Designing the Optimal Inhaled Product

Cited by 55 publications

References 55 publications

In Vitro Testing for Orally Inhaled Products: Developments in Science-Based Regulatory Approaches

In Vitro Testing for Orally Inhaled Products: Developments in Science-Based Regulatory Approaches

A Comparison of Drug Transport in Pulmonary Absorption Models: Isolated Perfused rat Lungs, Respiratory Epithelial Cell Lines and Primary Cell Culture

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

Contact Info

Product

Resources

About