Influence of crystal form of ipratropium bromide on micronisation and aerosolisation behaviour in dry powder inhaler formulations.
ABSTRACT 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.
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.
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 (R² = 0.998) and 0.77 (R² = 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.
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.
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ABSTRACT: Understanding the adhesive interactions between active pharmaceutical ingredient (API) particles and carrier particles in dry powder inhalers (DPIs) is critical for the development of formulations and process design. In the current study, a discrete element method, which accounts for particle adhesion, is employed to investigate the attachment processes in DPIs. A critical velocity criterion is proposed to determine the lowest impact velocity at which two elastic autoadhesive spherical particles will rebound from each other during impact. Furthermore, the process of fine API particles adhering to a large carrier in a vibrating container is investigated. It was found that there are optimal amplitude and frequency for the vibration velocity that can maximise the number of particles contacting with the carrier (i.e. the contact number). The impact number and detachment number during the vibration process both increase with increasing vibration amplitude and frequency while the sticking efficiency decreases as the amplitude and frequency are increased.Granular Matter 01/2013; · 1.50 Impact Factor