title: Optimization and dissolution performance of spray-dried naproxen nano-crystals.
abstract: The purpose of this study was to investigate the in vitro dissolution performance of the different sized spray-dried nano-crystalline powders of naproxen. A DoE approach was used to formulate and optimize nano-crystalline suspensions. The critical wet milling operation parameters were i.e., drug concentration, drug-to-stabilizer ratio, stabilizer type (HPMC E15 or Tween 80) and milling intensity. The nano-crystalline suspensions were optimized for size and physical stability and then spray-dried to obtain nano-crystalline powders. Trehalose and lactose were investigated as spray-drying auxiliary excipients to achieve non-aggregating powders. Particle size, DSC and PXRD were utilized for characterization of powder formulations. A modified USP apparatus II was utilized to determine the in vitro release/dissolution of powder formulations. The size of the nano-crystalline suspensions was dependent on drug concentration and milling intensity. HPMC E15 containing formulations were better in terms of the spray-dried powder yield compared to Tween 80 containing formulations. Trehalose was selected to formulate non-aggregating nano-crystalline powders. No polymorphic changes were observed following the wet milling and spray-drying processes. Size dependent in vitro dissolution profiles, utilizing a dialysis sac method were obtained for the crystalline powders.
authors: University of Connecticut, School of Pharmacy, 69 North Eagleville Road, Unit 3092, Storrs, CT 06269, USA.
authors: Sumit
authors: S
authors: Kumar
authors: University of Connecticut, School of Pharmacy, 69 North Eagleville Road, Unit 3092, Storrs, CT 06269, USA.
authors: Jie
authors: J
authors: Shen
authors: FDA/CDER/OPS, 10903 New Hampshire Ave, Silver Spring, MD 20993-0002, USA.
authors: Banu
authors: B
authors: Zolnik
authors: FDA/CDER/OPS, 10903 New Hampshire Ave, Silver Spring, MD 20993-0002, USA.
authors: Nakissa
authors: N
authors: Sadrieh
authors: University of Connecticut, School of Pharmacy, 69 North Eagleville Road, Unit 3092, Storrs, CT 06269, USA. Electronic address: d.burgess@uconn.edu.
authors: Diane J
authors: DJ
authors: Burgess
mesh_terms: D004339:Drug Compounding; D065347:Hypromellose Derivatives / Q000737:chemistry; D007785:Lactose / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D009288:Naproxen / Q000737:chemistry*; D010316:Particle Size; D011136:Polysorbates / Q000737:chemistry; D011208:Powders; D012995:Solubility; D014199:Trehalose / Q000737:chemistry
chemical_list: D011136:Polysorbates; D011208:Powders; D065347:Hypromellose Derivatives; D009288:Naproxen; D014199:Trehalose; D007785:Lactose
keywords: DoE; Nano-crystalline; Nano-suspension; Re-dispersion; Spray drying; Spray-dried powder