Towards Standardized Dissolution Techniques for In Vitro Performance Testing of Dry Powder Inhalers

Floroiu, Andreea; Klein, Martin J.; Krämer, Johannes; Lehr, Claus‐Michael

doi:10.14227/dt250318p6

Cited by 20 publications

(14 citation statements)

References 64 publications

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“…PBS was employed as the dissolution medium owing to its simple composition, better buffering effect and aptness for demonstrating sustained release characteristics or pH-dependent profile [ 66 ]. Further, the pH of PBS was fixed at 7.4 to reflect the pH of lung lining fluid [ 67 ].…”

Section: Discussionmentioning

confidence: 99%

Nebulised surface-active hybrid nanoparticles of voriconazole for pulmonary Aspergillosis demonstrate clathrin-mediated cellular uptake, improved antifungal efficacy and lung retention

et al. 2021

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Background Incidence of pulmonary aspergillosis is rising worldwide, owing to an increased population of immunocompromised patients. Notable potential of the pulmonary route has been witnessed in antifungal delivery due to distinct advantages of direct lung targeting and first-pass evasion. The current research reports biomimetic surface-active lipid-polymer hybrid (LPH) nanoparticles (NPs) of voriconazole, employing lung-specific lipid, i.e., dipalmitoylphosphatidylcholine and natural biodegradable polymer, i.e., chitosan, to augment its pulmonary deposition and retention, following nebulization. Results The developed nanosystem exhibited a particle size in the range of 228–255 nm and drug entrapment of 45–54.8%. Nebulized microdroplet characterization of NPs dispersion revealed a mean diameter of ≤ 5 μm, corroborating its deep lung deposition potential as determined by next-generation impactor studies. Biophysical interaction of LPH NPs with lipid-monolayers indicated their surface-active potential and ease of intercalation into the pulmonary surfactant membrane at the air-lung interface. Cellular viability and uptake studies demonstrated their cytocompatibility and time-and concentration-dependent uptake in lung-epithelial A549 and Calu-3 cells with clathrin-mediated internalization. Transepithelial electrical resistance experiments established their ability to penetrate tight airway Calu-3 monolayers. Antifungal studies on laboratory strains and clinical isolates depicted their superior efficacy against Aspergillus species. Pharmacokinetic studies revealed nearly 5-, 4- and threefolds enhancement in lung AUC, Tmax, and MRT values, construing significant drug access and retention in lungs. Conclusions Nebulized LPH NPs were observed as a promising solution to provide effective and safe therapy for the management of pulmonary aspergillosis infection with improved patient compliance and avoidance of systemic side-effects.

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Section: Discussionmentioning

confidence: 99%

Nebulised surface-active hybrid nanoparticles of voriconazole for pulmonary Aspergillosis demonstrate clathrin-mediated cellular uptake, improved antifungal efficacy and lung retention

et al. 2021

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“…Here, a Franz type cell with limited liquid volume in the donor compartment was adopted as dissolution method instead of the compendial USP Apparatus I, II or IV in order to keep the in vitro dissolution conditions closer to those present in the lung. In fact, the method adopted here, is one of the few capable to create an air-liquid interface which somehow resemble to what happens on the lung inner surfaces [71].…”

Section: Discussionmentioning

confidence: 99%

Sodium Hyaluronate Nanocomposite Respirable Microparticles to Tackle Antibiotic Resistance with Potential Application in Treatment of Mycobacterial Pulmonary Infections

et al. 2019

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Tuberculosis resistant cases have been estimated to grow every year. Besides Mycobacterium tuberculosis, other mycobacterial species are responsible for an increasing number of difficult-to-treat infections. To increase efficacy of pulmonary treatment of mycobacterial infections an inhalable antibiotic powder targeting infected alveolar macrophages (AMs) and including an efflux pump inhibitor was developed. Low molecular weight sodium hyaluronate sub-micron particles were efficiently loaded with rifampicin, isoniazid and verapamil, and transformed in highly respirable microparticles (mean volume diameter: 1 μm) by spray drying. These particles were able to regenerate their original size upon contact with aqueous environment with mechanical stirring or sonication. The in vitro drugs release profile from the powder was characterized by a slow release rate, favorable to maintain a high drug level inside AMs. In vitro antimicrobial activity and ex vivo macrophage infection assays employing susceptible and drug resistant strains were carried out. No significant differences were observed when the powder, which did not compromise the AMs viability after a five-day exposure, was compared to the same formulation without verapamil. However, both preparations achieved more than 80% reduction in bacterial viability irrespective of the drug resistance profile. This approach can be considered appropriate to treat mycobacterial respiratory infections, regardless the level of drug resistance.

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“…Particles used for the dissolution experiments were mainly collected from cascade impactors and dissolution in apparatus of the European Pharmacopoeia performed. Other collection methods and exposure set-ups have also been reported and been reviewed for instance by Floroiu et al [107].…”

Section: In Vitro Models To Assess Biological Processesmentioning

confidence: 99%

Biological Obstacles for Identifying In Vitro-In Vivo Correlations of Orally Inhaled Formulations

Frőhlich

2019

Pharmaceutics

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Oral inhalation of drugs is the classic therapy of obstructive lung diseases. In contrast to the oral route, the link between in vitro and in vivo findings is less well defined and predictive models and parameters for in vitro-in vivo correlations are missing. Frequently used in vitro models and problems in obtaining in vivo values to establish such models and to identify the action of formulations in vivo are discussed. It may be concluded that major obstacles to link in vitro parameters on in vivo action include lack of treatment adherence and incorrect use of inhalers by patients, variation in inhaler performance, changes by humidity, uncertainties about lung deposition, and difficulties to measure drug levels in epithelial lining fluid and tissue. Physiologically more relevant in vitro models, improvement in inhaler performance, and better techniques for in vivo measurements may help to better understand importance and interactions between individual in vitro parameters in pulmonary delivery.

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Towards Standardized Dissolution Techniques for In Vitro Performance Testing of Dry Powder Inhalers

Cited by 20 publications

References 64 publications

Nebulised surface-active hybrid nanoparticles of voriconazole for pulmonary Aspergillosis demonstrate clathrin-mediated cellular uptake, improved antifungal efficacy and lung retention

Nebulised surface-active hybrid nanoparticles of voriconazole for pulmonary Aspergillosis demonstrate clathrin-mediated cellular uptake, improved antifungal efficacy and lung retention

Sodium Hyaluronate Nanocomposite Respirable Microparticles to Tackle Antibiotic Resistance with Potential Application in Treatment of Mycobacterial Pulmonary Infections

Biological Obstacles for Identifying In Vitro-In Vivo Correlations of Orally Inhaled Formulations

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