title: smartCrystal combination technology--scale up from lab to pilot scale and long term stability.
abstract: The production of nanocrystals was scaled up from lab scale (20 g) to pilot scale (3 kg), scale up factor 150. The flavonoid apigenin was used as model compound, with potential for pharma, cosmetic and nutraceutical products. Lab scale production was performed by high pressure homogenization (HPH), pilot scale by applying the smartCrystal combination technology (CT), combining pearl milling and a subsequent HPH (1 cycle, 300 bar). The obtained particle sizes were compared on the basis of photon correlation spectroscopy (PCS), laser diffractometry (LD) and light microscopy. The results showed, that assessment of successful scale up depends on the characterization method used, e.g., PCS covering only a part of the particle size range (3 nm-3 microm) of the population, or LD the full size distribution. Long-term stability was predicted on zeta potential (ZP) measurements. Lab and pilot scale possessed sufficiently high ZP values (> 30 mV) for a stable dispersion, but the ZP values were different (5-7 mV). This was explained by differences in the Stern/Nernst potential of the nanocrystals, potentially due to different levels in the crystals where they break in a high energy process (HPH) versus a low energy size reduction (pearl mill). Independent on the production method and batch size, the nanosuspensions proved to be physically stable for 6 months at storage temperatures 4 degrees C, room temperature and 40 degrees C.
authors.affiliation: Department of Pharmaceutics, Biopharmaceutics & NutriCosmetics, Institute of Pharmacy, Berlin, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Al Shaal
authors.forename: R H
authors.initials: RH
authors.lastname: Müller
authors.forename: R
authors.initials: R
authors.lastname: Shegokar
mesh_terms: D047310:Apigenin / Q000737:chemistry; D003460:Crystallization; D004355:Drug Stability; D004563:Electrochemistry; D007834:Lasers; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D017785:Photons; D013057:Spectrum Analysis; D013535:Suspensions; D013678:Technology, Pharmaceutical; D013696:Temperature
chemical_list: D013535:Suspensions; D047310:Apigenin