TY - JOUR
T1 - Effects of thermal binders on chemical stabilities and tabletability of gabapentin granules prepared by twin-screw melt granulation
AU - Kittikunakorn, Nada
AU - Koleng, J. Joseph
AU - Listro, Tony
AU - Calvin Sun, Changquan
AU - Zhang, Feng
N1 - Funding Information:
The authors would like to thank Foster Delivery Science (Putnam, CT, USA) for the financial support of this study.
Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2019/3/25
Y1 - 2019/3/25
N2 - The effect of thermal binders on the physicochemical properties of gabapentin, a thermally labile drug, in granules prepared using twin-screw melt granulation was investigated in this study. Hydroxypropyl cellulose (HPC), a thermoplastic high molecular-weight binder, was compared against conventional low molecular-weight semi-crystalline thermal binders PEG 8000 and Compritol. Both the chemical degradation and polymorph form change of gabapentin were analyzed. The effects of particle size and molecular weight of HPC on the properties of granules were also studied. To overcome the high melt viscosity of HPC, higher barrel temperatures and higher specific mechanical energy were required to attain suitable granules. As a result, higher levels of gabapentin degradant were observed in HPC-based formulations. However, gabapentin form change was not observed in all formulations. Smaller particle size and lower molecular weight of HPC led to faster granule growth. The tabletability of granules was insensitive to the variations in particle size and molecular weight of HPC. Gabapentin crystal size reduction, HPC size reduction, and HPC enrichment on granule surface were observed for HPC-based granules.
AB - The effect of thermal binders on the physicochemical properties of gabapentin, a thermally labile drug, in granules prepared using twin-screw melt granulation was investigated in this study. Hydroxypropyl cellulose (HPC), a thermoplastic high molecular-weight binder, was compared against conventional low molecular-weight semi-crystalline thermal binders PEG 8000 and Compritol. Both the chemical degradation and polymorph form change of gabapentin were analyzed. The effects of particle size and molecular weight of HPC on the properties of granules were also studied. To overcome the high melt viscosity of HPC, higher barrel temperatures and higher specific mechanical energy were required to attain suitable granules. As a result, higher levels of gabapentin degradant were observed in HPC-based formulations. However, gabapentin form change was not observed in all formulations. Smaller particle size and lower molecular weight of HPC led to faster granule growth. The tabletability of granules was insensitive to the variations in particle size and molecular weight of HPC. Gabapentin crystal size reduction, HPC size reduction, and HPC enrichment on granule surface were observed for HPC-based granules.
KW - Continuous manufacturing
KW - Gabapentin
KW - Hydroxypropyl cellulose
KW - Tabletability
KW - Twin-screw melt granulation
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U2 - 10.1016/j.ijpharm.2019.01.014
DO - 10.1016/j.ijpharm.2019.01.014
M3 - Article
C2 - 30660749
AN - SCOPUS:85060629999
SN - 0378-5173
VL - 559
SP - 37
EP - 47
JO - International journal of pharmaceutics
JF - International journal of pharmaceutics
ER -