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

Abstract

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.

Interaction of Formulation and Device Factors Determine the In Vitro Performance of Salbutamol Sulphate Dry Powders for Inhalation

“…Mechanistically, the intrinsic level of lactose fines in Respitose ML006 may have saturated the active sites or formed a layer over the coarse carrier to reduce direct contact between the drug and coarse carrier . Intrinsic fines facilitate the formation of mixed agglomerates without the requirement for the addition of extra fine lactose particles …”

“…28 Intrinsic fines facilitate the formation of mixed agglomerates without the requirement for the addition of extra fine lactose particles. 34 It was apparent that the formulation dispersal and emission was poorer for the Rotahaler as the level of (intrinsic or extrinsic) fines increased (e.g., comparing ED (%) for LHF0 and M6F0 in Table 3), probably because of different powder microstructures forming depending on fines content. The enhancement of FPF by by addition of fine lactose to Lactohale LH200 and Respitose ML001 did not occur with all devices.…”

On the Breakage of High Aspect Ratio Crystals in Filter Beds under Continuous Percolation

“…For crystals in these regions the particle area based on pixels equals to A pix = L × W. The red regions show clusters of overlapping particles for which the pixel based statistics are not representative of individual particles (A pix ≪ L × W) and should thus not be used in statistics describing particle distribution. A number of authors have used the Morphologi G3 alongside laser diffraction techniques in order to characterise particle shape factors (31)(32)(33)(34)(35)(36). They confirm that the particle size measured by Morphologi G3 tends to be larger than those measured under diffraction due to the presence of overlapping particles (34,36).…”

On the effects of blending, physicochemical properties, and their interactions on the performance of carrier-based dry powders for inhalation — A review

“…10a). It is arguable that fine excipient particulates influence the dispersion of adhesive mixtures through a combination of all the latter mechanisms [176], among which the dominant mechanism is determined by the choice of several interacting variables such as blending conditions, formulation physicochemical properties, carrier payload, and aerosolisation conditions. For example, the effect of fine particulate excipients on DPI performance was shown to be strongly dependent on the type of inhaler device [30].…”