Enhancement of inhaled micronized powder flow properties for accurate capsules filling

Dry powder inhalerCapsule fillingLung deliveryAdhesive mixtureInhalation powderInterparticle interaction forces; dry powder inhaler; capsule filling; lung delivery; adhesive mixture; inhalation powder; interparticle interaction forces

Abstract :

[en] Particle engineering holds significant promise in developing high-performance inhaled powders. The spray-drying technology leads to the optimization of particle properties, enhancing aerosolization capabilities. However, the development of such inhalation powders introduces challenges related to cohesive forces due to, among others, the small particle size. Our study aims to find an easy industrial method for improving powder flow properties to facilitate the handling of these powders, especially in the context of capsules or reservoir filling. To achieve this, we focus on adhesive blends of micronized spray-dried powder, which includes budesonide and formoterol, with coarse lactose excipient. It is intended to develop a homogeneous blend without overly strong interparticular interactions that could potentially compromise the final pulmonary deposition of micronized powders. Two lactose grades, namely Inhalac 70 and Inhalac 230, were tested in various proportions with spray-dried powder. For both lactose grades, the 50:50 mixture demonstrated homogeneity over 8 weeks, exhibiting no signs of segregation. Importantly, the forces within the blend enable optimal aerosolization, as similar performance has been observed compared to spray-dried powder alone. Subsequently, the improvement in flowability, leading to improved reproducibility in the capsule filling process, was evaluated using an industrial prototype filler (Drum TT). While achieving uniform capsule mass remained challenging with the cohesive spray-dried powder alone, the 50:50 mixtures induced compliant capsule filling. Moreover, impaction tests demonstrated comparable in vitro lung deposition compared to manually filled capsules. We further explored the impact of inhaler device resistance and airflow conditions during the impaction assay on aerosolization properties. Our research revealed the feasibility of blending micronized powder with lactose to facilitate the handling of this powder during industrial processes without compromising aerodynamic performance. Moving forward, these formulations exhibit potential for scalable industrial applications in pulmonary drug delivery.

Disciplines :

Pharmacy, pharmacology & toxicology

Author, co-author :

Gresse, Eva ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM)

Rousseau, Justine

Akdim, Myriam

Du Bois, Audrey

Lechanteur, Anna ; Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique

Evrard, Brigitte ; Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique

Language :

English

Title :

Enhancement of inhaled micronized powder flow properties for accurate capsules filling

Publication date :

27 February 2024

Journal title :

Powder Technology

ISSN :

0032-5910

eISSN :

1873-328X

Publisher :

Elsevier BV

Issue :

119576

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://api.elsevier.com/content/article/PII:S0032591024002183?httpAccept=text/xml

Available on ORBi :

since 30 March 2024

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