The Influence of Lung Deposition on Clinical Response

Pritchard, J.N.

doi:10.1089/08942680150506303

Cited by 164 publications

(86 citation statements)

References 10 publications

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“…47 The relative importance of total lung deposition vs regional lung deposition, and how this influences both beneficial effects and side effects of inhaled drugs, is incompletely understood. 48 Since APSD is the most significant characteristic determining deposition in the respiratory tract and deposition influences clinical response, APSD must predict clinical response to inhaled drugs, at least to some degree. 49 For an inhaled corticosteroid, a 4-fold change in dose may be needed in order to detect a difference in clinical response.…”

Section: Apsd Deposition and Clinical Effectsmentioning

confidence: 99%

In vitro and in vivo aspects of cascade impactor tests and inhaler performance: A review

2007

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The purpose of this review is to discuss the roles of cascade impactor (CI) data in inhaler assessment and to examine the relationship between aerodynamic particle size distribution (APSD) and the clinical response to inhaled drugs. A systematic literature search of studies linking APSD to clinical response was undertaken. Two distinct roles for CI-generated data were identified: (1) the control of inhaler/drug product quality; and (2) the provision of data that may be predictive of particle deposition in the respiratory tract. Method robustness is required for the former application, combined with simplicity in operation, resulting in rudimentary attempts to mimic the anatomy of the respiratory tract. The latter necessitates making the apparatus and its operation more closely resemble patient use of the inhaler. A CI cannot perfectly simulate the respiratory tract, since it operates at constant flow rate, while the respiratory cycle has a varying flow-time profile. On the basis of a review of studies linking APSD to clinical response of inhaled drugs, it is concluded that attempts to use CIgenerated data from quality control testing to compare products for bioequivalence are likely to have only limited success, as links between laboratory-measured APSD, particle deposition in the respiratory tract, and clinical response are not straightforward.

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Section: Apsd Deposition and Clinical Effectsmentioning

confidence: 99%

In vitro and in vivo aspects of cascade impactor tests and inhaler performance: A review

2007

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“…4) The aerodynamic size of drug particles should be 5-6 µm or less for optimal airway deposition. [5][6][7] However, particles in this size range have potentially cohesive property and tend to disperse poorly.…”

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confidence: 99%

Spray Freeze-Dried Porous Microparticles of a Poorly Water-Soluble Drug for Respiratory Delivery

Niwa

Mizutani

Danjo

2012

CHEMICAL & PHARMACEUTICAL BULLETIN

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Particles of poorly water-soluble drugs were prepared to develop a dry powder inhaler (DPI). Spray freeze-drying (SFD) technique using a four-fluid nozzle (4N), which has been developed by authors, was applied in this research. Ciclosporin and mannitol were used as a poorly water-soluble model drug and a dissolution-enhanced carrier, respectively. The organic solution of ciclosporin and aqueous solution of mannitol were separately and simultaneously atomized through the 4N, and the two solutions were collided with each other at the tip of the nozzle edge. The spray mists were immediately frozen in liquid nitrogen to form a suspension. Then, the iced droplets were freeze-dried to prepare the composite particles of the drug and carrier. tert-Butyl alcohol (t-BuOH) was used as the organic spray solvent due to its relatively high freezing point. The resultant composite particles with varying drug content were characterized depending on their morphological and physicochemical properties. The particles contained amorphous ciclosporin and δ-crystalline mannitol. The characteristic porous structure of SFD particles potentially contributed to their good aerodynamic performance. A series of particles with a similar size distribution and different drug content revealed that the incorporation of mannitol successfully improved the cohesive behavior of ciclosporin, leading to enhanced aerosol dispersion. The dissolution test method using low-volume medium was newly established to simulate the release process from particles deposited on the surface of the bronchus and pulmonary mucosa. The composite with hydrophilic mannitol dramatically improved the in vitro dissolution behavior of ciclosporin in combination with the porous structure of SFD particles.Key words spray freeze-drying; liquid nitrogen; ciclosporin; porous particle; tert-butyl alcohol Inhalation is the most appropriate route to deliver drugs to treat respiratory disorders such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis.1-3) This route directly targets the site of action and reduces the occurrence of systemic adverse effects. In addition, there is increasing interest in the use of pulmonary delivery to administer systemically-acting macromolecules, such as inhaled insulin product.4) The aerodynamic size of drug particles should be 5-6 µm or less for optimal airway deposition.5-7) However, particles in this size range have potentially cohesive property and tend to disperse poorly.One approach to achieve excellent inhalation delivery by simultaneously improving the micromeritic properties and reducing the cohesive properties of agents is to design spherical particles with relative large geometric diameters and low particle mass densities. Inter-particulate cohesion could be reduced by enlarging and spheronizing the individual particle, and aerosol performance could be improved by decreasing the weight of the particles, ultimately like soap bubbles. In particular, particle design focused on particle density has been specifically resear...

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“…95% CIs for the relative potency were computed according to Fieller's theorem. Equivalence was to be concluded if the 90% CI calculated for the log (relative potency) was within 0.67 -1.50 [28]. Table 1 shows the baseline demographics of the study populations.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Pharmacokinetic and Pharmacodynamic Effects of Two Hydrofluoroalkane Formulations of Salmeterol

Morde¹,

Rebello²,

Brashier³

et al. 2017

J Bioequiv Availab

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The Influence of Lung Deposition on Clinical Response

Cited by 164 publications

References 10 publications

In vitro and in vivo aspects of cascade impactor tests and inhaler performance: A review

In vitro and in vivo aspects of cascade impactor tests and inhaler performance: A review

Spray Freeze-Dried Porous Microparticles of a Poorly Water-Soluble Drug for Respiratory Delivery

Comparison of Pharmacokinetic and Pharmacodynamic Effects of Two Hydrofluoroalkane Formulations of Salmeterol

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