The permeability of large molecular weight solutes following particle delivery to air-interfaced cells that model the respiratory mucosa

Grainger, C.; Greenwell, Leona L.; Martin, GP; Forbes, Ben

doi:10.1016/j.ejpb.2008.09.006

Cited by 77 publications

(74 citation statements)

References 20 publications

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“…Deposition of particles generated by each formulation onto the cell layers and measurement of transepithelial BDP flux was conducted using methods adapted from Grainger et al [10,17]. In this method, the twin stage impinger (TSI) (Radleys, Essex, UK) was modified to accommodate a Transwell insert in the lower chamber.…”

Section: In Vitro Cell Deposition Studiesmentioning

confidence: 99%

Towards the bioequivalence of pressurised metered dose inhalers 2. Aerodynamically equivalent particles (with and without glycerol) exhibit different biopharmaceutical profiles in vitro

Haghi

Bebawy

Colombo

et al. 2014

European Journal of Pharmaceutics and Biopharmaceutics

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a b s t r a c tTwo solution-based pressurised metered dose inhaler (pMDI) formulations were prepared such that they delivered aerosols with identical mass median aerodynamic diameters, but contained either beclomethasone dipropionate (BDP) alone (glycerol-free formulation) or BDP and glycerol in a 1:1 mass ratio (glycerol-containing formulation). The two formulations were deposited onto Calu-3 respiratory epithelial cell layers cultured at an air interface. Equivalent drug mass ($1000 ng or $2000 ng of the formulation) or equivalent particle number (1000 ng of BDP in the glycerol-containing versus 2000 ng of BDP in the glycerol-free formulation) were deposited as aerosolised particles on the air interfaced surface of the cell layers. The transfer rate of BDP across the cell layer after deposition of the glycerol-free particles was proportional to the mass deposited. In comparison, the transfer of BDP from the glycerol-containing formulation was independent of the mass deposited, suggesting that the release of BDP is modified in the presence of glycerol. The rate of BDP transfer (and the extent of metabolism) over 2 h was faster when delivered in glycerol-free particles, 465.01 ng ± 95.12 ng of the total drug (20.99 ± 4.29%; BDP plus active metabolite) transported across the cell layer, compared to 116.17 ng ± 3.07 ng (6.07 ± 0.16%) when the equivalent mass of BDP was deposited in glycerol-containing particles. These observations suggest that the presence of glycerol in the maturated aerosol particles may influence the disposition of BDP in the lungs.

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Section: In Vitro Cell Deposition Studiesmentioning

confidence: 99%

Towards the bioequivalence of pressurised metered dose inhalers 2. Aerodynamically equivalent particles (with and without glycerol) exhibit different biopharmaceutical profiles in vitro

Haghi

Bebawy

Colombo

et al. 2014

European Journal of Pharmaceutics and Biopharmaceutics

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“…Whilst particle cutoff diameter and regional lung deposition are not precise, in an anatomical sense, these pharmacopeia approaches still give some indication of regional lung deposition. Prior to testing, 7 mL of water was added to stage 1 of the TSI and stage 2 was modified as described previously to accommodate a Transwell assembly (19). The TSI was adjusted to a flow rate of 60 L min −1 using a rotary vein pump and solenoid timer (Copley Scientific, Nottingham, UK) in combination with a calibrated flow meter (TSI, 4000 series, Buckinghamshire, UK) to which an Aerolizer® DPI device (Novartis, Surrey, UK) was attached to the inlet of the flow meter to account for the pressure drop across the device.…”

Section: Physicochemical Characterisation Of the Dscg And Dscg/pva MImentioning

confidence: 99%

“…The aerosolisation and deposition of drug onto the air interface model was conducted in a similar manner to the TSI studies described previously (19). Briefly, the method followed that of Grainger et al, where the TSI was modified to incorporate the Transwell insert at the stage 2 jet assembly (no liquid was added to stage 2).…”

Section: Drug Aerosol Deposition and Uptake Studiesmentioning

confidence: 99%

“…Furthermore, the cell line can be cultured in two configurations-as a liquid-covered model or as an air interface model-where the latter closely mimics airway epithelia with respect to cell differentiation, polarisation, the presence of microvilli and mucus secretion (13). In addition, the latter model can be incorporated into a modified in vitro impaction apparatus so that the deposition of representative aerosolised particle formulations can be evaluated (11,19,20). To evaluate drug transport kinetics in this study, dry powder formulations of respirable size were deposited onto the Calu-3 cellular model according to the assembly described by Grainger et al (19).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, the latter model can be incorporated into a modified in vitro impaction apparatus so that the deposition of representative aerosolised particle formulations can be evaluated (11,19,20). To evaluate drug transport kinetics in this study, dry powder formulations of respirable size were deposited onto the Calu-3 cellular model according to the assembly described by Grainger et al (19).…”

Section: Introductionmentioning

confidence: 99%

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Modification of Disodium Cromoglycate Passage Across Lung Epithelium In Vitro Via Incorporation into Polymeric Microparticles

Haghi

Salama

Traini

et al. 2011

AAPS J

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Abstract. Two microparticle systems containing disodium cromoglycate (DSCG) alone or with polyvinyl alcohol (DSCG/PVA) were produced via spray drying and compared in terms of their physicochemical characteristics, aerosol performance and drug uptake across a pulmonary epithelial cell line (Calu-3), cultured under air interface conditions. The particle size distribution of DSCG and DSCG/PVA were similar, of spherical geometry, amorphous and suitable for inhalation purposes. Aerosolisation studies using a modified twin-stage impinger showed the DSCG/PVA to have greater aerosol performance than that of DSCG alone. Aerosol particles of DSCG and DSCG/PVA were deposited onto the surface of the Calu-3 air interface epithelium monolayer and the drug uptake from apical to basal directions measured over time. Drug uptake was measured across a range of doses to allow comparison of equivalent drug and powder mass deposition. Analysis of the data indicated that the percentage cumulative drug uptake was independent of the mass of powder deposited, but dependent on the formulation. Specifically, with the formulation containing DSCG, the diffusion rate was observed to change with respect to time (indicative of a concentration-dependent diffusion process), whilst DSCG/PVA showed a time-independent drug uptake (suggesting a zero-order depot release).

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In VitroDissolution for Inhalation Products

Mercuri¹,

Fotaki²

2019

In Vitro Drug Release Testing of Special Dosage Forms

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The permeability of large molecular weight solutes following particle delivery to air-interfaced cells that model the respiratory mucosa

Cited by 77 publications

References 20 publications

Towards the bioequivalence of pressurised metered dose inhalers 2. Aerodynamically equivalent particles (with and without glycerol) exhibit different biopharmaceutical profiles in vitro

Towards the bioequivalence of pressurised metered dose inhalers 2. Aerodynamically equivalent particles (with and without glycerol) exhibit different biopharmaceutical profiles in vitro

Modification of Disodium Cromoglycate Passage Across Lung Epithelium In Vitro Via Incorporation into Polymeric Microparticles

In VitroDissolution for Inhalation Products

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