Accelerated ketoprofen release from spray-dried polymeric particles: importance of phase transitions and excipient distribution

Abstract

HPMC-, PVPVA- and PVP-based microparticles loaded with 30% ketoprofen were prepared by spray drying suspensions or solutions in various water:ethanol blends. The inlet temperature, drying gas and feed flow rates were varied. The resulting differences in the ketoprofen release rates in 0.1 M HCl could be explained based on X-ray diffraction, mDSC, SEM and particle size analysis. Importantly, long term stable drug release could be provided, being much faster than: (i) drug release from a commercial reference product, (ii) the respective physical drug:polymer mixtures, as well as (iii) the dissolution of ketoprofen powder as received. In addition, highly supersaturated release media were obtained, which did not show any sign for re-crystallization during the observation period. Surprisingly, spraying suspensions resulted in larger microparticles exhibiting faster drug release compared to spraying solutions, which resulted in smaller particles exhibiting slower drug release. These effects could be explained based on the physico-chemical characteristics of the systems.

• Dissolution
• HPMC
• ketoprofen
• poorly soluble drugs
• spray-drying

Acknowledgements

The authors are grateful for the support of this work by the French National Research Agency “ANR” (ACROHNEM), the Nord-Pas de Calais Regional Council (PRIM) and the “INTERREG IVA 2 Mers Seas Zeeën Cross-border Cooperation Programme 2007–2013” (IDEA).

Declaration of interest

The authors report no declarations of interest.