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.
- Journal of Pharmaceutical Sciences 11/1971; 60(10):1559-64. · 3.13 Impact Factor
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ABSTRACT: To investigate the anomalous phenomenon of particle size shift during post-milling storage. Crystallised and ball-milled adipic acid were stored under different humidity conditions. Analyses were carried out to characterise changes in particle size distribution (laser diffraction), morphology (SEM), bulk flow properties (annular shear tester), surface adhesion forces (AFM) and crystallinity (PXRD and DVS). It was observed that the particle size distribution of milled adipic acid can shift to finer fractions, remain unchanged, or even shift to coarser fractions depending on storage conditions. SEM analysis showed that milled adipic acid is composed of agglomerates, which can undergo de-aggregation or further agglomeration via re-crystallisation. Empirical analysis ruled out the effects of electrostatic charges on the particle size shift. In addition, an improvement in powder flow in terms of bulk tensile strength was seen for milled adipic acid stored under high relative humidity but not under low humidity. Storage of milled adipic acid below the critical relative humidity led to localised disintegration from the agglomerate surface and particle size reduction, which was not influenced by moisture sorption or loss. This evidence supports that "stress relaxation" mechanism behind particle breakage of post-milled particles. Appropriate storage conditions are important in maintaining the stability of milled powders.Pharmaceutical Research 06/2008; 25(5):1175-85. · 4.74 Impact Factor
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ABSTRACT: To investigate the influence of primary crystallization conditions on the mechanical properties and secondary processing behaviour of fluticasone propionate (FP) for carrier based dry powder inhaler (DPI) formulations. Young's modulus of FP crystals produced using different anti-solvents was determined using nanoindentation. Physicochemical and surface interfacial properties via the cohesive-adhesive balance (CAB) approach to colloid probe atomic force microscopy (AFM) of air-jet micronised FP crystals were investigated. These data were correlated to in vitro aerosolization performance of binary and combination DPI formulations containing salmeterol xinafoate (SX). Young's modulus of FP crystals produced using different anti-solvents ranged from 0.6-12.4 GPa. Crystals with low Young's modulus required multiple passes in the microniser to reduce the particle size to less than 5 μm, whilst those with the highest Young's modulus required a single pass. CAB of micronized FP samples was similar with respect to lactose, however, their adhesive affinity to SX varied. Samples of FP with greatest adhesion to SX produced greater fine particle delivery of SX in combination DPI formulations. Crystallisation conditions may affect the mechanical properties of FP, and therefore secondary processing of the material and their interfacial properties and product performance in carrier based DPI formulations.Pharmaceutical Research 12/2011; 29(4):994-1006. · 4.74 Impact Factor