TY - JOUR
T1 - Simultaneous micronization and surface modification for improvement of flow and dissolution of drug particles
AU - Han, Xi
AU - Ghoroi, Chinmay
AU - To, Daniel
AU - Chen, Yuhua
AU - Davé, Rajesh
N1 - Funding Information:
The authors gratefully acknowledge the financial support from the National Science Foundation (NSF) through grant EEC-0540855 . The authors would also like to thank Stefan Steigerwald and George Foster from Sympatec, NJ, for particle size analysis at the beginning of this research; Tim Freeman for providing a FT4 powder rheometer; Prof. Ecevit Bilgili for his valuable suggestions and Dr. Costas Gogos for providing access to the FEM and the dissolution tester during initial phase of this study.
PY - 2011/8/30
Y1 - 2011/8/30
N2 - 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.
AB - 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.
KW - Co-grinding
KW - Dissolution rate
KW - Dry coating
KW - Flowability
KW - Fluid energy mill (FEM)
KW - Micronization
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U2 - 10.1016/j.ijpharm.2011.05.070
DO - 10.1016/j.ijpharm.2011.05.070
M3 - Article
C2 - 21664954
AN - SCOPUS:79960185799
SN - 0378-5173
VL - 415
SP - 185
EP - 195
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1-2
ER -