Hot melt mixing and foaming of soluplus® and indomethacin

Polymer Engineering and Science - Tập 52 Số 8 - Trang 1629-1639 - 2012
Graciela Terife1, Peng Wang2, Niloufar Faridi3, Costas G. Gogos4,3
1Materials Science and Engineering Program, New Jersey Institute of Technology, Newark, New Jersey 07102
2Department of Chemical Engineering, University of Rhode Island, Kingston, Rhode Island, 02881
3Polymer Processing Institute, Newark, New Jersey 07102
4Otto H. York Department of Chemical, Biological, and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, New Jersey 07102

Tóm tắt

AbstractThe hot melt mixing (HMM) process was used to dissolve 30 wt% of a model drug, indomethacin (INM), in Soluplus® a water soluble polymer excipient. Comprehensive characterization of the HMM‐prepared samples, using differential scanning calorimetry, X‐ray diffraction, Fourier Transform Infrared spectroscopy, and optical microscopy, strongly suggests that INM was in amorphous state, forming a solid solution with the polymer. Furthermore, to understand the impact of foaming on INM's release profile, the HMM product was foamed in a batch process using supercritical carbon dioxide (CO2). Dissolution tests of HMM and reference samples were conducted in aqueous solutions with pH 7.4 and 1.2. In all cases INM's release showed strong pH‐dependency; faster release and a greater amount of INM was released at pH 7.4 than at pH 1.2. For pure INM and the physical mixture, the drug's ionizable character results in the observed pH‐dependency. While for the HMM samples it is also a consequence of theformation of hydrogen bonds between Soluplus® and INM which hinder polymer dissolution at pH 1.2. It was observed that the release rate of INM from different sample types at pH 7.4 decreased in the following sequence: foamed HMM > unfoamed HMM > crystalline INM > physical mixture. POLYM. ENG. SCI., 2012. © 2012 Society of Plastics Engineers

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Tài liệu tham khảo

10.1016/j.ijpharm.2010.04.033

Liu H., 2010, York, Hot Melt Mixing/Extrusion and dissolution of drug (Indomethacin) in Acrylic copolymer matrices. PhD Thesis. Department of Chemical, Biological and Pharmaceutical Engineering

10.1016/j.ijpharm.2009.09.003

Hardung H., 2010, Drug Deliv. Technol., 10, 20

10.1016/j.ejps.2005.07.006

10.1016/j.ijpharm.2006.07.024

10.1016/j.supflu.2006.05.005

10.1016/j.supflu.2005.11.022

Brown C.D., 2011, ANTEC 2011, 1224

10.1016/j.jconrel.2006.07.018

10.1016/S0928-0987(02)00223-3

10.1016/S0378-5173(01)00617-2

10.1111/j.2042-7158.2010.01177.x

J.BreitenbachandH.Baumgartl U.S. Patent 09/254 012(2000).

A.J.Clarke US Patent 10/500 630(2005).

10.1023/B:PHAM.0000016242.48642.71

10.1016/S0939-6411(00)00076-X

10.1016/j.ijpharm.2007.11.048

10.1021/js970137w

10.1016/j.ijpharm.2010.10.026

10.1002/jps.20385

10.1002/jps.21174

10.1021/ma100662x

10.1080/03639040701498759

Sears J.K., 1985, Encyclopedia of Polymer Science and Engineering

10.1016/j.ejpb.2007.11.001

10.1021/bm049213x

10.1016/j.ijpharm.2006.03.035

10.1023/A:1011979221685

10.1023/A:1012167410376

10.1039/b103498g

10.1016/S0032-3861(96)00550-2

10.1016/S0378-5173(98)00159-8

10.1021/ie50599a029

10.1021/ma00222a013

10.1016/S0168-3659(00)00303-5

10.1002/jps.21138

Terife G., 2011, Foams

10.1016/0378-5173(89)90126-9

10.1007/s11095-006-9085-3

10.1016/j.ejpb.2004.06.007

FDA 1997 FDA Rockville

10.1023/A:1011976615750

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Polymer Engineering and Science

Tập 52 Số 8

1629-1639

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