Accelerated ketoprofen release from spray-dried polymeric particles: importance of phase transitions and excipient distribution.
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.
College of Pharmacy, University of Lille , Lille , France .
Emilie
E
Gue
Susanne
S
Muschert
Jean-Francois
JF
Willart
Florence
F
Danede
Elisabeth
E
Delcourt-Debruyne
Marc
M
Descamps
Juergen
J
Siepmann
D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization; D065546:Drug Liberation; D005079:Excipients / Q000737:chemistry*; D065347:Hypromellose Derivatives / Q000737:chemistry; D007660:Ketoprofen / Q000008:administration & dosage* / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D044367:Phase Transition; D011108:Polymers / Q000737:chemistry*; D011205:Povidone / Q000031:analogs & derivatives / Q000737:chemistry; D012995:Solubility; D013696:Temperature; D014961:X-Ray Diffraction
D005079:Excipients; D011108:Polymers; C549547:vinylacetate-vinylpyrrolidone copolymer; D065347:Hypromellose Derivatives; D007660:Ketoprofen; D011205:Povidone
Dissolution; HPMC; ketoprofen; poorly soluble drugs; spray-drying