TY - JOUR
T1 - Dry coating of micronized API powders for improved dissolution of directly compacted tablets with high drug loading
AU - Han, Xi
AU - Ghoroi, Chinmay
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 like to thank Dr. David Harris for suggesting blend formulation, Mr. Matthew Mullarney for his input in tablet formation, Dr. Edward Dreyzin for providing access to the Instron, Dr. Daniel To for useful discussions, Freeman Technology for comments regarding the FT4 rheometer results for the blends, and BASF for providing the gift samples of Kollodon- CL.
PY - 2013/2/14
Y1 - 2013/2/14
N2 - Motivated by our recent study showing improved flow and dissolution rate of the active pharmaceutical ingredient (API) powders (20 μm) produced via simultaneous micronization and surface modification through continuous fluid energy milling (FEM) process, the performance of blends and direct compacted tablets with high drug loading is examined. Performance of 50 μm API powders dry coated without micronization is also considered for comparison. Blends of micronized, non-micronized, dry coated or uncoated API powders at 30, 60 and 70% drug loading, are examined. The results show that the blends containing dry coated API powders, even micronized ones, have excellent flowability and high bulk density compared to the blends containing uncoated API, which are required for direct compaction. As the drug loading increases, the difference between dry coated and uncoated blends is more pronounced, as seen in the proposed bulk density-FFC phase map. Dry coating led to improved tablet compactibility profiles, corresponding with the improvements in blend compressibility. The most significant advantage is in tablet dissolution where for all drug loadings, the t80 for the tablets with dry coated APIs was well under 5 min, indicating that this approach can produce nearly instant release direct compacted tablets at high drug loadings.
AB - Motivated by our recent study showing improved flow and dissolution rate of the active pharmaceutical ingredient (API) powders (20 μm) produced via simultaneous micronization and surface modification through continuous fluid energy milling (FEM) process, the performance of blends and direct compacted tablets with high drug loading is examined. Performance of 50 μm API powders dry coated without micronization is also considered for comparison. Blends of micronized, non-micronized, dry coated or uncoated API powders at 30, 60 and 70% drug loading, are examined. The results show that the blends containing dry coated API powders, even micronized ones, have excellent flowability and high bulk density compared to the blends containing uncoated API, which are required for direct compaction. As the drug loading increases, the difference between dry coated and uncoated blends is more pronounced, as seen in the proposed bulk density-FFC phase map. Dry coating led to improved tablet compactibility profiles, corresponding with the improvements in blend compressibility. The most significant advantage is in tablet dissolution where for all drug loadings, the t80 for the tablets with dry coated APIs was well under 5 min, indicating that this approach can produce nearly instant release direct compacted tablets at high drug loadings.
KW - API blends
KW - Direct compaction
KW - Dissolution
KW - Dry coating
KW - Fine API powders
KW - Flowability
KW - Ibuprofen
KW - Micronization
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U2 - 10.1016/j.ijpharm.2012.08.004
DO - 10.1016/j.ijpharm.2012.08.004
M3 - Article
C2 - 22921376
AN - SCOPUS:84873407674
SN - 0378-5173
VL - 442
SP - 74
EP - 85
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1-2
ER -