TY - JOUR
T1 - Impact of polymeric excipient on cocrystal formation via hot-melt extrusion and subsequent downstream processing
AU - Karimi-Jafari, Maryam
AU - Ziaee, Ahmad
AU - Iqbal, Javed
AU - O'Reilly, Emmet
AU - Croker, Denise
AU - Walker, Gavin
N1 - Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2019/7/20
Y1 - 2019/7/20
N2 - Pharmaceutical cocrystals have gained increasing interest due to their potential to modify the physicochemical properties of drugs. Herein, a 1:1 cocrystal of ibuprofen (IBU) as a BCS class II active pharmaceutical ingredient (API) and nicotinamide as coformer was produced using a hot-melt extrusion (HME) process. The effect of process parameters such as barrel temperature and screw speed were studied. It was shown that the addition of polymeric excipient such as soluplus (Sol) decreases the cocrystallization temperature by enhancing the interaction between API and coformer. In order to study the effect of cocrystallization on the tableting properties of IBU-NIC cocrystal, 5 different formulations of pure IBU, IBU-NIC cocrystal, IBU-NIC physical mixture, IBU-NIC-Sol physical mixture and IBU-NIC-Sol cocrystal were tableted by a compaction simulator. Tabletability, compactibility and compressibility were investigated. The sample with IBU-NIC-Sol cocrystal formulation outperformed all the other formulations in terms of tabletability, compactibility and compressibility. Interestingly, this sample was even superior to the IBU-NIC cocrystal sample which verified the advantageous effect of the presence of an excipient. Moreover, dissolution test confirmed a noticeable increase in the dissolution of not only the cocrystal samples but even the physical mixtures of IBU and NIC compared with pure IBU.
AB - Pharmaceutical cocrystals have gained increasing interest due to their potential to modify the physicochemical properties of drugs. Herein, a 1:1 cocrystal of ibuprofen (IBU) as a BCS class II active pharmaceutical ingredient (API) and nicotinamide as coformer was produced using a hot-melt extrusion (HME) process. The effect of process parameters such as barrel temperature and screw speed were studied. It was shown that the addition of polymeric excipient such as soluplus (Sol) decreases the cocrystallization temperature by enhancing the interaction between API and coformer. In order to study the effect of cocrystallization on the tableting properties of IBU-NIC cocrystal, 5 different formulations of pure IBU, IBU-NIC cocrystal, IBU-NIC physical mixture, IBU-NIC-Sol physical mixture and IBU-NIC-Sol cocrystal were tableted by a compaction simulator. Tabletability, compactibility and compressibility were investigated. The sample with IBU-NIC-Sol cocrystal formulation outperformed all the other formulations in terms of tabletability, compactibility and compressibility. Interestingly, this sample was even superior to the IBU-NIC cocrystal sample which verified the advantageous effect of the presence of an excipient. Moreover, dissolution test confirmed a noticeable increase in the dissolution of not only the cocrystal samples but even the physical mixtures of IBU and NIC compared with pure IBU.
KW - Cocrystal
KW - Compactibility
KW - Compaction triangle
KW - Compressibility
KW - Downstream processing
KW - Hot-melt extrusion
KW - Tabletability
UR - http://www.scopus.com/inward/record.url?scp=85067419048&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2019.06.031
DO - 10.1016/j.ijpharm.2019.06.031
M3 - Article
C2 - 31212053
AN - SCOPUS:85067419048
SN - 0378-5173
VL - 566
SP - 745
EP - 755
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
ER -