Influence of Physicochemical Properties of Crospovidone Grades on their Performance in Extrusion-Spheronizatio

Pellets are successful oral solid dosage forms that offer simplicity in production and have high patient compliance; moreover, smaller pellets have an advantage over larger tablets due to decreased gastric retention time. It has been reported that crospovidone, a hydrophilic cross-linked homopolymer of N-vinyl pyrrolidone is a suitable alternative to microcrystalline cellulose (MCC) that is considered the gold standard excipient for the production of pellets. It was also observed that KollidonRTM CL - SF (KCLSF), a crospovidone product from BASF, fails to produce pellets although it was expected to perform similarly to its market equivalents, Polyplasdone RTM XL-10 (PXL-10) or INF-10 from Ashland Inc. due to similarities in their particle sizes and chemistry.;The use of fine particle ethylcellulose (FPEC) and poly(ethylene oxide) (PEO) as extrusion aids for KCLSF was investigated along with formulation and process variables that are expected to contribute to pellet characteristics. The inclusion of PEO in the study was inspired by the failure of FPEC, a known extrusion aid, to facilitate production of pellets as the optimization of each of the pellet characteristics as a function of experimental variables was deemed unsuccessful. The addition of PEO resulted in the production of characterizable pellets such that optimum levels for formulation and process variables could be established using an experimental design approach. Further investigation was carried out on the performance of several crospovidone grades in dynamic vapor sorption analysis (DVSA), extrusion-spheronization, and mixer torque rheometry (MTR) in light of other morphological differences such as density, porosity and pore size distribution revealed using helium pycnometry and mercury intrusion porosimetry.;DVSA revealed comparable uptake and hysteresis behavior for various crospovidone grades; however, internalized water was greater with KCLSF, owing to its higher porosity. Although it has been suggested that one of the possible reasons for the failure of KCLSF in extrusion-spheronization is its very high water requirement (about 200% w/w) to achieve a decent torque value, this does not entirely explain why KCLSF fails. The loss of KCLSF wetted mass in extrusion is due to its poor binding ability at the high water levels typically required by this grade of crospovidone. Addition of a hydrophilic extrusion aid, PEO, lowers the water requirement for an appropriate wetted mass and also imparts added cohesiveness to the system resulting in its success as a wetted mass in extrusion-spheronization.