Investigation into the influence of primary crystallization conditions on the mechanical properties and secondary processing behaviour of fluticasone propionate for carrier based dry powder inhaler formulations

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

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Purpose:
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.
Methods:
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).
Results:
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.
Conclusions:
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.
Original languageEnglish
Pages (from-to)994-1006
Number of pages13
JournalPharmaceutical Research
Volume29
Issue number4
Early online date9 Dec 2011
DOIs
Publication statusPublished - 30 Apr 2012

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