Influence of crystal form of ipratropium bromide on micronisation and aerosolisation behaviour in dry powder inhaler formulations

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

Research output: Contribution to journalArticlepeer-review

11 Citations (SciVal)


Objectives: This study aimed to investigate the relationship between the mechanical properties of anhydrous and monohydrate ipratropium bromide (IB) crystals, their processing behaviour upon air-jet micronisation and aerosolisation performance in dry powder inhaler (DPI) formulations.
Methods: IB monohydrate and anhydrous crystals were produced from seed crystals and supercritical carbon dioxide crystallisation, respectively. Young's modulus of anhydrous and monohydrate IB crystals was determined using nanoindentation. For air-jet micronised crystals, the physicochemical and surface interfacial properties via the cohesive-adhesive balance (CAB) approach were investigated. These data were correlated to in-vitro aerosolisation performance of carrier-based DPI formulations containing either anhydrous or monohydrate IB.
Key findings: Particle size and Young's modulus of both crystals were similar and this was reflected in their similar processing upon micronisation. Particle size of micronised anhydrous and monohydrate crystals were similar. CAB measurements of the micronised particles of monohydrate or anhydrous forms of IB with respect to lactose were 0.70 (R 2=0.998) and 0.77 (R 2=0.999), respectively. These data suggested that both samples had similar adhesion to lactose, which correlated with their similar in-vitro aerosolisation performance in DPI formulations.
Conclusions: Monohydrate and anhydrous crystals of IB exhibited similar mechanical properties and interfacial properties upon secondary processing. As a result, the performance of the DPI formulations were similar.

Original languageEnglish
Pages (from-to)1326-1336
Number of pages11
JournalJournal of Pharmacy and Pharmacology
Issue number9
Early online date13 May 2012
Publication statusPublished - Sept 2012


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