The Cohesive-Adhesive Balances in Dry Powder Inhaler Formulations II: Influence on Fine Particle Delivery Characteristics

Begat, Philippe; Morton, David Alexander Vodden; Staniforth, John N.; Price, Robert

doi:10.1023/b:pham.0000045236.60029.cb

Cited by 117 publications

(75 citation statements)

References 8 publications

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“…Fine particle lactose added as carrier material improved the fluidisation as shown by a shift in the CAB ratio. The study further demonstrated that not only the disaggregation and deposition of the drug itself but also the stability during manufacturing and handling are affected by the CAB ratio within the system (Begat et al, 2004b).…”

Section: Cohesive Adhesive Balance (Cab)mentioning

confidence: 79%

“…The plot shows whether a system is dominated by adhesive or cohesive forces which is important for the development of DPI formulations as agglomeration and segregation, and therefore the fluidisation and dispersion properties of the powder, are affected by the CAB ratio (Begat et al, 2004b). Begat et al (2004a) made use of the colloid probe technique to observe the CAB ratio in DPI formulations of salbutamol sulphate and budesonide with the carrier material lactose.…”

Section: Cohesive Adhesive Balance (Cab)mentioning

confidence: 99%

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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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Section: Cohesive Adhesive Balance (Cab)mentioning

confidence: 79%

Section: Cohesive Adhesive Balance (Cab)mentioning

confidence: 99%

Characterisation of dry powder inhaler formulations using atomic force microscopy

Weiss

McLoughlin

Cathcart

2015

International Journal of Pharmaceutics

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“…In contrast, however, the effect of the API particle size on in vitro aerosolization performance was not so obvious. In DPI formulation systems, API surface interfacial properties are known to affect drug product performance (13,17,29,30). Traditionally, the surface interfacial properties of APIs have been measured indirectly through measurement of amorphous content or surface free energy (31,32).…”

Section: Discussionmentioning

confidence: 99%

“…Particle size, particle morphology, surface roughness and interfacial chemistry of the API and carrier particles have been shown to play a key role in determining these interfacial interactions (9)(10)(11)(12)(13)(14). Whilst the surface and interfacial properties of the API are known to be critical in controlling product performance of DPI products, the primary property characterized for the API component of DPI formulations remains to be the particle size.…”

Section: Electronic Supplementary Materialsmentioning

confidence: 99%

“…Thus, for product development, the surface and interfacial properties of the API should warrant a greater degree of characterization in order to ensure consistent performance of a DPI product. For instance, the cohesive-adhesive balance (CAB) approach, determined via colloid probe measurements using atomic force microscopy (AFM), has provided the ability to understand and optimize the characteristics of carrier-based DPI formulations through quantification of the balance of inter-particulate forces of the API within DPI systems (13,(15)(16)(17). This information on the API is key to achieving in vitro comparability of test and reference DPI products.…”

Section: Electronic Supplementary Materialsmentioning

confidence: 99%

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Effect of Device Design and Formulation on the In Vitro Comparability for Multi-Unit Dose Dry Powder Inhalers

Shur

Saluja

Lee

et al. 2015

AAPS J

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Abstract. The focus of this investigation was to understand the design space to achieve comparable in vitro performance of two multi-unit dose dry powder inhalers (DPIs)-Flixotide® Accuhaler® (reference product) and MultiHaler® (test product). Flow field, pressure drop and particle trajectories within the test and reference DPI devices were modelled via computational fluid dynamics (CFD). Micronized fluticasone propionate (FP) was characterized to determine particle size distribution (PSD), specific surface area (SSA) and surface interfacial properties using cohesive-adhesive balance (CAB). CFD simulations suggested that the pressure drop and airflow velocity in the MultiHaler® were greater than Accuhaler®. Two modified test devices (MOD MH 1 and MOD MH 2) were manufactured with the introduction of by-pass channels in the airflow path, which achieved comparable specific resistance and airflow path between the test and reference devices. Assessment of reference product formulation in modified test devices suggested that MOD MH 2 achieved comparable in vitro performance to the reference product. CAB analysis suggested that adhesion of all FP batches to lactose was different, with batch D showing greatest and batch A least adhesion to lactose. Test DPI formulations were manufactured using four different batches of FP with milled or sieved lactose, and showed that batch A FP formulated with sieved lactose in MOD MH 2 device demonstrated the highest degree of similarity to the Accuhaler® in vitro deposition. Application of CFD modelling and material characterization of formulation raw materials enabled the modification of device and formulation critical material attributes to create an in vitro comparable device/formulation system to the reference product.KEY WORDS: aerosolization; computational fluid dynamics; device design; dry powder inhaler; in vitro comparability; in vitro performance.

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Aerosol Drug Delivery

Hindle

2010

Pharmaceutical Sciences Encyclopedia

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Aerosol drug delivery to the lungs has long been the route of choice for the treatment of respiratory diseases, including asthma and chronic obstructive airway disease. Metered dose inhalers (MDIs), dry powder inhalers (DPIs), and nebulizers have been employed to successfully deliver a wide range of pharmaceuticals principally to the lungs for local action. This article focuses on aerosol drug delivery devices, their development, and future prospects for pulmonary administration.

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The Cohesive-Adhesive Balances in Dry Powder Inhaler Formulations II: Influence on Fine Particle Delivery Characteristics

Cited by 117 publications

References 8 publications

Characterisation of dry powder inhaler formulations using atomic force microscopy

Characterisation of dry powder inhaler formulations using atomic force microscopy

Effect of Device Design and Formulation on the In Vitro Comparability for Multi-Unit Dose Dry Powder Inhalers

Aerosol Drug Delivery

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