Influence of primary crystallisation conditions on the mechanical and interfacial properties of micronised budesonide for dry powder inhalation

Kubavat, Harshal A.; Shur, Jagdeep; Ruecroft, Graham; Hipkiss, David; Price, Robert

doi:10.1016/j.ijpharm.2012.03.020

Cited by 19 publications

(12 citation statements)

References 37 publications

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“…These data highlight the subtle nature of surface interfacial free energy of the DPI formulation components, which, in turn, may affect the performance of the final drug product (33). Hence, it is essential to understand the relationship between material processing and its influence on the physicochemical properties to formulate DPI drug products with desired performance characteristics.…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…Micronized budesonide (Sterling S.r.l, Perugia, Italy) was used as received. The cohesive-adhesive balance (CAB) value for the sourced micronized budesonide was determined as 0.62 following a method described elsewhere (26), implying that the drug preferentially adhered to the lactose, with the interaction being 38% greater than the drug-drug interaction. Methanol and acetonitrile were of HPLC grade (Fisher Scientific, Loughborough, UK), and water was reverse osmosis purified.…”

Section: Methodsmentioning

confidence: 99%

An Investigation into the Effect of Fine Lactose Particles on the Fluidization Behaviour and Aerosolization Performance of Carrier-Based Dry Powder Inhaler Formulations

Kinnunen

Hebbink²,

Peters³

et al. 2014

AAPS PharmSciTech

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Abstract. The effect of milled and micronized lactose fines on the fluidization and in vitro aerosolization properties of dry powder inhaler (DPI) formulations was investigated, and the suitability of static and dynamic methods for characterizing general powder flow properties of these blends was assessed. Lactose carrier pre-blends were prepared by adding different lactose fines (Lactohale® (LH) 300, 230 and 210) with coarse carrier lactose (Lactohale100) at 2.5, 5, 10 and 20 wt% concentrations. Powder flow properties of lactose pre-blends were characterized using the Freeman Technology FT4 and Schulze RST-XS ring shear tester. A strong correlation was found between the basic flow energy (BFE Norm ) measured using the Freeman FT4 Rheometer and the flowability number (ff c ) measured on Schulze RST-XS. These data indicate that both static and dynamic methods are suitable for characterizing general powder flow properties of lactose carriers. Increasing concentration of fines corresponded with an increase in the normalized fluidization energy (FE Norm ). The inclusion of fine particles of lactose resulted in a significant (p<0.05) increase in fine particle delivery of budesonide and correlated with FE Norm . This trend was strongest for lactose containing up to 10 wt% LH300. A similar trend was found for the milled lactose grades LH230 and LH210. However, the increase in FE Norm upon addition of milled fines only corresponded to a very slight improvement in the performance. These data suggest that whilst the fluidization energy correlated with fine particle delivery, this relationship is specific to lactose grades of similar particle size.

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“…A Cyclohaler device (Teva Pharmaceuticals, The Netherlands) was used for aerosolising the formulations into a Next Generation Impactor (NGI, Copley Scientific, Nottingham, UK) equipped with a pre-separator. Air was drawn through the impactor at 90 l/min for 2.7 seconds (Kubavat et al, 2012) as controlled by a TPK critical flow controller (also from Copley Scientific). Two capsules were aerosolised into the impactor with plates coated with silicone oil and the pre-separator filled with 15 ml of mobile phase.…”

Section: In Vitro Assessment Of Formulation Performancementioning

confidence: 99%

“…The concentration of budesonide collected in the different parts of the impactor was assessed using high performance liquid chromatography (HPLC) following a method reported elsewhere (Kubavat et al, 2012). Briefly, the samples were dissolved in mobile phase consisting of 20% water, 35% acetonitrile and 45% methanol.…”

Section: High Performance Chromatography (Hplc) Assay Of Budesonidementioning

confidence: 99%

Extrinsic lactose fines improve dry powder inhaler formulation performance of a cohesive batch of budesonide via agglomerate formation and consequential co-deposition

Kinnunen

Hebbink²,

Peters³

et al. 2015

International Journal of Pharmaceutics

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Price, R. (2015) 'Extrinsic lactose nes improve dry powder inhaler formulation performance of a cohesive batch of budesonide via agglomerate formation and consequential co-deposition.', International journal of pharmaceutics., 478 (1). pp. 53-59. Further information on publisher's website:http://dx.doi.org/10.1016/j.ijpharm.2014.11.019Publisher's copyright statement: NOTICE: this is the author's version of a work that was accepted for publication in International Journal of Pharmaceutics. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be re ected in this document. Changes may have been made to this work since it was submitted for publication. A de nitive version was subsequently published in International Journal of Pharmaceutics, 478, 1, 15 January 2015, 10.1016/j.ijpharm.2014 Additional information: Use policyThe full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-pro t purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. AbstractThe aim of the study was to investigate how the fine particle content of lactose carriers prepared with different types of lactose fines regulates dry powder inhaler (DPI) formulation performance of a cohesive batch of micronised budesonide.Budesonide formulations (0.8 wt-% ) were prepared with three different lactose carriers (Lactohale (LH) LH100, 20 wt-% LH210 in LH100 and 20 wt-% LH300 in LH100 indicated that the more fine lactose particles were available the more agglomerates of budesonide and lactose were delivered to the Stage 2. These results suggest drug-fines agglomerate formation is an important mechanism for how lactose fines improve and regulate DPI formulation performance.

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Influence of primary crystallisation conditions on the mechanical and interfacial properties of micronised budesonide for dry powder inhalation

Cited by 19 publications

References 37 publications

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

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

An Investigation into the Effect of Fine Lactose Particles on the Fluidization Behaviour and Aerosolization Performance of Carrier-Based Dry Powder Inhaler Formulations

Extrinsic lactose fines improve dry powder inhaler formulation performance of a cohesive batch of budesonide via agglomerate formation and consequential co-deposition

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