title: Nanosuspensions of poorly soluble drugs: preparation and development by wet milling.
abstract: Nanosizing techniques are important tools for improving the bioavailability of water insoluble drugs. Here, a rapid wet milling method was employed to prepare nanosuspensions: 4 types of stabilizers at 4 different concentrations were tested on 2 structurally different drug compounds: indomethacin and itraconazole. Photon correlation spectroscopy (PCS) results showed that the finest nanosuspensions were obtained when 80 wt% (to drug amount) pluronic F68 was the stabilizer for indomethacin and 60 wt% pluronic F127 for itraconazole. Compared to physical mixtures, dissolution rates of the nanosuspensions showed significant increases. The morphology of nanoparticles was observed by transmission electron microscopy (TEM). Crystalline state of the drugs before and after milling was confirmed using differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD). The physical and chemical stabilities of the nanosuspensions after storage for 2 months at room temperature and at 4°C were investigated using PCS, TEM and HPLC. No obvious changes in particle size and morphology and no chemical degradation of the drug ingredients were seen.
authors: Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, PO Box 56, 00014 Helsinki, Finland. peng.liu@helsinki.fi
authors: Peng
authors: P
authors: Liu
authors: Xinyu
authors: X
authors: Rong
authors: Johanna
authors: J
authors: Laru
authors: Bert
authors: B
authors: van Veen
authors: Juha
authors: J
authors: Kiesvaara
authors: Jouni
authors: J
authors: Hirvonen
authors: Timo
authors: T
authors: Laaksonen
authors: Leena
authors: L
authors: Peltonen
mesh_terms: D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D004339:Drug Compounding / Q000379:methods*; D016503:Drug Delivery Systems; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D007213:Indomethacin / Q000737:chemistry; D017964:Itraconazole / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D020442:Poloxamer / Q000737:chemistry; D012995:Solubility; D013535:Suspensions / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D005079:Excipients; D004364:Pharmaceutical Preparations; D013535:Suspensions; D014867:Water; D020442:Poloxamer; D017964:Itraconazole; D007213:Indomethacin