TY - JOUR

T1 - Improvement of the physicochemical properties of Co-amorphous naproxen-indomethacin by naproxen-sodium

AU - Beyer, Andreas

AU - Grohganz, Holger

AU - Löbmann, Korbinian

AU - Rades, Thomas

AU - Leopold, Claudia S

N1 - Copyright © 2017 Elsevier B.V. All rights reserved.

PY - 2017/6/30

Y1 - 2017/6/30

N2 - Improvement of the physicochemical properties of amorphous active pharmaceutical ingredients (APIs) applying the concept of co-amorphisation is a promising alternative to the use of polymer glass solutions. In co-amorphous systems, the physical stability and the dissolution rate of the involved components may be improved in comparison to the respective single amorphous phases. However, for the co-amorphous naproxen-indomethacin model system it has been reported that recrystallization could not be prevented for more than 112days regardless of the applied preparation method and blend ratio In the present study, it was thus tested if the physicochemical properties of co-amorphous naproxen-indomethacin could be optimized by incorporation of the naproxen sodium into the system. Three different co-amorphous systems in nine different molar ratios were prepared by quench-cooling: naproxen-indomethacin (NI), naproxen-sodium-naproxen-indomethacin (NSNI) and naproxen-sodium-indomethacin (NSI). The samples were analyzed by XRPD, FTIR, DSC and by intrinsic dissolution experiments to investigate the influence of naproxen-sodium on the resulting physicochemical properties of the systems. With the three systems, fully amorphous samples with single glass transition temperatures could be prepared with naproxen molar fractions up to 0.7. The NSI and NSNI systems showed up to about 40°C higher Tgs than the NI system. Furthermore, no recrystallization occurred during 270d of storage with the NSI and NSNI samples that were initially amorphous. Moreover, with the NSI system, the intrinsic dissolution rate of naproxen and indomethacin was improved by a factor of 2 compared to the unmodified NI system. In conclusion, the physical stability as well as the dissolution rate was significantly improved if partial or full exchange of naproxen by its sodium salt was performed, which may present a general optimization method to improve co-amorphous systems.

AB - Improvement of the physicochemical properties of amorphous active pharmaceutical ingredients (APIs) applying the concept of co-amorphisation is a promising alternative to the use of polymer glass solutions. In co-amorphous systems, the physical stability and the dissolution rate of the involved components may be improved in comparison to the respective single amorphous phases. However, for the co-amorphous naproxen-indomethacin model system it has been reported that recrystallization could not be prevented for more than 112days regardless of the applied preparation method and blend ratio In the present study, it was thus tested if the physicochemical properties of co-amorphous naproxen-indomethacin could be optimized by incorporation of the naproxen sodium into the system. Three different co-amorphous systems in nine different molar ratios were prepared by quench-cooling: naproxen-indomethacin (NI), naproxen-sodium-naproxen-indomethacin (NSNI) and naproxen-sodium-indomethacin (NSI). The samples were analyzed by XRPD, FTIR, DSC and by intrinsic dissolution experiments to investigate the influence of naproxen-sodium on the resulting physicochemical properties of the systems. With the three systems, fully amorphous samples with single glass transition temperatures could be prepared with naproxen molar fractions up to 0.7. The NSI and NSNI systems showed up to about 40°C higher Tgs than the NI system. Furthermore, no recrystallization occurred during 270d of storage with the NSI and NSNI samples that were initially amorphous. Moreover, with the NSI system, the intrinsic dissolution rate of naproxen and indomethacin was improved by a factor of 2 compared to the unmodified NI system. In conclusion, the physical stability as well as the dissolution rate was significantly improved if partial or full exchange of naproxen by its sodium salt was performed, which may present a general optimization method to improve co-amorphous systems.

KW - Journal Article

U2 - 10.1016/j.ijpharm.2017.04.011

DO - 10.1016/j.ijpharm.2017.04.011

M3 - Journal article

C2 - 28392278

VL - 526

SP - 88

EP - 94

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

IS - 1-2

ER -