title: Simultaneous micronization and surface modification for improvement of flow and dissolution of drug particles.
abstract: Simultaneous micronization and surface modification of drug particles is considered in order to mitigate disadvantages of micronization, e.g., agglomeration, poor flowability, marginal increase in surface area and low bulk density. Particles of ibuprofen (102 μm), a model drug, pre-blended with hydrophilic nano-silica, are micronized down to 10 and 5 μm in a continuous fluid energy mill (FEM) to obtain fine surface modified particles. The solid feeding rate and the grinding pressure are shown as critical parameters for achieving the desired particle size and size distribution. The powder properties were characterized via SEM, laser scattering, powder rheometer with shear-cell, and dissolution test. Significant improvement in flow properties and dissolution rate was observed when micronization accompanied surface modification. Additionally, co-grinding with water-soluble polymer during micronization led to further increase in bulk density and more enhanced dissolution rate improvement, which is attributed to improved wettability. XRD, DSC and Raman were used to examine crystallinity, indicating minimal detectable physical transformation with FEM processed ibuprofen. The surface modified, micronized powders also showed improved dispersion, higher bulk densities (>0.4 g/ml), reduced electrostatic, and higher flowability (FFC ≥ 6) compared to just micronized powder (0.19 g/ml, FFC=1.0), indicating they may be used in high drug loaded formulations amenable to direct compression.
authors.affiliation: New Jersey Center for Engineered Particulates, New Jersey Institute of Technology, Newark, NJ 07102, USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Han
authors.forename: Chinmay
authors.initials: C
authors.lastname: Ghoroi
authors.forename: Daniel
authors.initials: D
authors.lastname: To
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Chen
authors.forename: Rajesh
authors.initials: R
authors.lastname: Davé
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry; D003460:Crystallization; D004867:Equipment Design; D007052:Ibuprofen / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D033362:Powder Diffraction; D011208:Powders; D012212:Rheology; D012995:Solubility; D013059:Spectrum Analysis, Raman; D013314:Stress, Mechanical; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods* / Q000592:standards; D014961:X-Ray Diffraction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004364:Pharmaceutical Preparations; D011208:Powders; D007052:Ibuprofen