Particle Engineering for Pulmonary Drug Delivery

Chow, Albert H.L.; Tong, Henry H.Y.; Chattopadhyay, Pratibhash; Shekunov, Boris Y.

doi:10.1007/s11095-006-9174-3

Cited by 573 publications

(410 citation statements)

References 199 publications

(229 reference statements)

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“…use of a recirculation flow cell to better control the fabrication process [24,28]). Furthermore, the technique in its current form could be useful for the micronization of minute amount of drugs (for potential application in pulmonary delivery [29]) as it would then generate less degradation products. …”

Section: Bioavailability Studymentioning

confidence: 99%

Nanonization of megestrol acetate by laser fragmentation in aqueous milieu

Sylvestre

Tang

Fürtös

et al. 2011

Journal of Controlled Release

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Nanonization is a simple and effective method to improve dissolution rate and oral bioavailability of drugs with poor water solubility. There is growing interest to downscale the nanocrystal production to enable early preclinical evaluation of new drug candidates when compound availability is scarce. The purpose of the present study was to investigate laser fragmentation to form nanosuspensions in aqueous solution of the insoluble model drug megestrol acetate (MA) using very little quantities of the drug. Laser fragmentation was obtained by focusing a femtosecond (fs) or nanosecond (ns) laser radiation on a magnetically stirred MA suspension in water or aqueous solution of a stabilizing agent. The size distribution and physicochemical properties of the drug nanoparticles were characterized, and the in vitro dissolution and in vivo oral pharmacokinetics of a laser fragmented formulation were evaluated. A MA nanosuspension was also prepared by media milling for comparison purpose. For both laser radiations, smaller particles were obtained as the laser power was increased, but at a cost of higher degradation. Significant nanonization was achieved after a 30-min fs laser treatment at 250 mW and a 1-h ns laser treatment at 2500 mW. The degradation induced by the laser process of the drug was primarily oxidative in nature. The crystal phase of the drug was maintained, although partial loss of crystallinity was observed. The in vitro dissolution rate and in vivo bioavailability of the laser fragmented formulation were similar to those obtained with the nanosuspension prepared by media milling, and significantly improved compared to the coarse drug powder. It follows that this laser nanonization method has potential to be used for the preclinical evaluation of new drug candidates.

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Section: Bioavailability Studymentioning

confidence: 99%

Nanonization of megestrol acetate by laser fragmentation in aqueous milieu

Sylvestre

Tang

Fürtös

et al. 2011

Journal of Controlled Release

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“…The DPI aerosol cloud should be constituted by particles with aerodynamic diameters between 1 and 3 µm with good dispersibility (good flow) to efficiently deliver the drugA c c e p t e d M a n u s c r i p t 4 into the lower (alveolar) regions of the lungs (Johnson, 1997;Koushik and Kompella, 2004;Chow et al, 2007). Ní Ógáin et al (2011) studied the in vitro deposition of spray dried trehalose and raffinose NPMPs powders using the Andersen Cascade Impactor (ACI).…”

Section: Introductionmentioning

confidence: 99%

Optimisation of spray drying process conditions for sugar nanoporous microparticles (NPMPs) intended for inhalation

Amaro

Tajber

Corrigan

et al. 2011

International Journal of Pharmaceutics

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The present study investigated the effect of operating parameters of a laboratory spray dryer on powder characteristics, in order to optimise the production of trehalose and raffinose powders, intended to be used as carriers of biomolecules for inhalation.The sugars were spray dried from 80:20 methanol:n-butyl acetate (v/v) solutions using a 30Büchi Mini Spray dryer B-290. A 2 4 factorial design of experiment (DOE) was undertaken. Process parameters studied were inlet temperature, gas flow rate, feed solution flow rate (pump setting) and feed concentration. Resulting powders where characterised in terms of yield, particle size (PS), residual solvent content (RSC) and outlet temperature. An additional outcome evaluated was the specific surface area 35 (SSA) (by BET gas adsorption), and a relation between SSA and the in vitro deposition of the sugar NPMPs powders was also investigated.The DOE resulted in well fitted models. The most significant factors affecting the characteristics of the NPMPs prepared, at a 95% confidence interval, were gas flow:yield, PS and SSA; pump setting: yield; inlet temperature: RSC. 40Raffinose NPMPs presented better characteristics than trehalose NPMPs in terms of their use for inhalation, since particles with larger surface area resulting in higher fine particle fraction can be produced. 45

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“…The drug load itself also affects formulation performance along with the choice of inhaler device (De Boer et al, 2005) and the patient's individual breathing pattern (Chrystyn and Price, 2009;Heyder, 2004). The relationship between particulate characteristics and their respective effects on formulation performance have been studied and reviewed widely over the years (Adi et al, 2013;Chan, 2008;Chow et al, 2007;Donovan and Smyth, 2010;Guenette et al, 2009;Healy et al, 2014;Zellnitz et al, 2014;Zeng et al, 2000;Zhang et al, 2011).…”

Section: Pulmonary Drug Deliverymentioning

confidence: 99%

Characterisation of dry powder inhaler formulations using atomic force microscopy

Weiss

McLoughlin

Cathcart

2015

International Journal of Pharmaceutics

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A B S T R A C TInhalation formulations are a popular way of treating the symptoms of respiratory diseases. The active pharmaceutical ingredient (API) is delivered directly to the site of action within the deep lung using an inhalation device such as the dry powder inhaler (DPI).The performance of the formulation and the efficiency of the treatment depend on a number of factors including the forces acting between the components. In DPI formulations these forces are dominated by interparticulate interactions. Research has shown that adhesive and cohesive forces depend on a number of particulate properties such as size, surface roughness, crystallinity, surface energetics and combinations of these. With traditional methods the impact of particulate properties on interparticulate forces could be evaluated by examining the bulk properties. Atomic force microscopy (AFM), however, enables the determination of local surface characteristics and the direct measurement of interparticulate forces using the colloidal probe technique. AFM is considered extremely useful for evaluating the surface topography of a substrate (an API or carrier particle) and even allows the identification of crystal faces, defects and polymorphs from high-resolution images. Additionally, information is given about local mechanical properties of the particles and changes in surface composition and energetics. The assessment of attractive forces between two bodies is possible by using colloidal probe AFM.This review article summarises the application of AFM in DPI formulations while specifically focussing on the colloidal probe technique and the evaluation of interparticulate forces.2015 Elsevier B.V. All rights reserved.

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Particle Engineering for Pulmonary Drug Delivery

Cited by 573 publications

References 199 publications

Nanonization of megestrol acetate by laser fragmentation in aqueous milieu

Nanonization of megestrol acetate by laser fragmentation in aqueous milieu

Optimisation of spray drying process conditions for sugar nanoporous microparticles (NPMPs) intended for inhalation

Characterisation of dry powder inhaler formulations using atomic force microscopy

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