TY - JOUR
T1 - Continuous preparation of polymer coated drug crystals by solid hollow fiber membrane-based cooling crystallization
AU - Chen, Dengyue
AU - Singh, Dhananjay
AU - Sirkar, Kamalesh K.
AU - Pfeffer, Robert
N1 - Funding Information:
The authors gratefully acknowledge support for this research from the US National Science Foundation through Grant CMMI-1100622 . We thank the Bristol-Myers Squibb Corporation (BMS), and especially Dr. San Kiang of BMS, for providing us with an industrial perspective.
Publisher Copyright:
© 2016 Elsevier B.V. All rights reserved.
PY - 2016/2/29
Y1 - 2016/2/29
N2 - A facile way to continuously coat drug crystals with a polymer is needed in controlled drug release. Conventional polymer coating methods have disadvantages: high energy consumption, low productivity, batch processing. A novel method for continuous polymer coating of drug crystals based on solid hollow fiber cooling crystallization (SHFCC) is introduced here. The drug acting as the host particle and the polymer for coating are Griseofulvin (GF) and Eudragit RL100, respectively. The polymer's cloud point temperature in its acetone solution was determined by UV spectrophotometry. An acetone solution of the polymer containing the drug in solution as well as undissolved drug crystals in suspension were pumped through the tube side of the SHFCC device; a cold liquid was circulated in the shell side to rapidly cool down the feed solution-suspension in the hollow-fiber lumen. The polymer precipitated from the solution and coated the suspended crystals due to rapid temperature reduction and heterogeneous nucleation; crystals formed from the solution were also coated by the polymer. Characterizations by scanning electron microscopy, thermogravimetric analysis, laser diffraction spectroscopy, X-ray diffraction, Raman spectroscopy, and dissolution tests show that a uniformly coated, free-flowing drug/product can be obtained under appropriate operating conditions without losing the drug's pharmaceutical properties and controlled release characteristics.
AB - A facile way to continuously coat drug crystals with a polymer is needed in controlled drug release. Conventional polymer coating methods have disadvantages: high energy consumption, low productivity, batch processing. A novel method for continuous polymer coating of drug crystals based on solid hollow fiber cooling crystallization (SHFCC) is introduced here. The drug acting as the host particle and the polymer for coating are Griseofulvin (GF) and Eudragit RL100, respectively. The polymer's cloud point temperature in its acetone solution was determined by UV spectrophotometry. An acetone solution of the polymer containing the drug in solution as well as undissolved drug crystals in suspension were pumped through the tube side of the SHFCC device; a cold liquid was circulated in the shell side to rapidly cool down the feed solution-suspension in the hollow-fiber lumen. The polymer precipitated from the solution and coated the suspended crystals due to rapid temperature reduction and heterogeneous nucleation; crystals formed from the solution were also coated by the polymer. Characterizations by scanning electron microscopy, thermogravimetric analysis, laser diffraction spectroscopy, X-ray diffraction, Raman spectroscopy, and dissolution tests show that a uniformly coated, free-flowing drug/product can be obtained under appropriate operating conditions without losing the drug's pharmaceutical properties and controlled release characteristics.
KW - Drug crystals
KW - Membrane-based cooling crystallization
KW - Polymer coating
KW - Solid hollow fiber
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U2 - 10.1016/j.ijpharm.2016.01.008
DO - 10.1016/j.ijpharm.2016.01.008
M3 - Article
C2 - 26772536
AN - SCOPUS:84955245852
SN - 0378-5173
VL - 499
SP - 395
EP - 402
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1-2
ER -