Effects of thermal binders on chemical stabilities and tabletability of gabapentin granules prepared by twin-screw melt granulation

Twin-Screw Melt Granulation for Oral Solid Pharmaceutical Products

“…Use of a larger binder particle size results in more granulation fines when compared with smaller particle size binder. Often, use of higher molecular weight binders correlates with larger granule size [ 48 , 49 ]. This converse effect can be attributed to the mechanism of binder distribution within the extruder.…”

“…Prior to processing, miscibility can be tested using differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) to look for changes in melting point or peaks in the mixture when compared with the pure drug [ 49 , 59 ]. DSC can be used to select processing temperatures to avoid API melting [ 8 , 47 , 49 , 57 , 59 , 62 , 65 , 68 , 69 , 70 ]. Additionally, hot-stage polarized light microscopy can provide visualization of any crystalline dissolution in liquid binder by maintaining elevated temperatures on a drug-binder binary mixture [ 49 ].…”

“…DSC can be used to select processing temperatures to avoid API melting [ 8 , 47 , 49 , 57 , 59 , 62 , 65 , 68 , 69 , 70 ]. Additionally, hot-stage polarized light microscopy can provide visualization of any crystalline dissolution in liquid binder by maintaining elevated temperatures on a drug-binder binary mixture [ 49 ]. Visible change in size and shape of API crystals can indicate miscibility between the drug and binder.…”

“…Rheometers are used to measure the viscosity of the binder as a function of temperature to properly select the binder and target processing temperature [ 47 ]. Melt rheometers provide further understanding of binder behavior and performance, providing target temperature for optimal binder processing [ 49 ]. Rheoscopes can be used to visually observe the behavior of binders and formulation systems as a function of temperature and shear, giving further insight into binder behavior, granulation mechanism, and potential miscibility [ 70 , 75 ].…”

“…HPC granules were the most compactible, but the API in PEG 8000 and Compritol granules degraded less. API degradation in the HPC granules was linked to the higher thermal and mechanical stresses with higher required process temperature [ 49 ] and further related to mechanical energy input and API particle attrition [ 60 ].…”