The evaluation of formulations for the preparation of pellets with high drug loading by extrusion/spheronization.
A capillary rheometer was used to evaluate rheological properties and the fluid mobility of mixtures with a high drug loading (80%) of three model drugs (ibuprofen, lactose, and ascorbic acid) when extruded. These drugs have a range of solubility in water, with 20% microcrystalline cellulose (MCC) as the spheronization aid, and water, pH 2.0, and pH 10.0 buffer as the binder liquid. The results were compared with the ability of the systems to form spherical pellets by the process of extrusion/spheronization. It was found possible to produce round pellets with a narrow size distribution by the process of extrusion/spheronization for formulations containing 80% of either lactose or ascorbic acid with MCC as the spheronization aid. It was not, however, possible to form pellets containing the same level of ibuprofen. This appears to be associated with the high level of fluid mobility observed when the wet masses were extruded in a ram extruder. A range of rheological characteristics in terms of shear stress, die entry pressure, angles of convergence, extensional flow, and elasticity were determined, but the variations in the values of these, which were observed, did not give an indication of the ability of the wet mass to form spherical pellets when subjected to the spheronization process. This could be associated with the fact that the selection of the conditions necessary to provide a valid quantification of the extrusion process did not truly represent the stability of the systems in terms of the mobility of the fluid when the wet mass was processed. The formulation of a wet mass with limited fluid mobility appears to be the first priority of formulations used in extrusion/spheronization.
Podczeck
Fridrun
F
School of Health, Natural & Social Sciences, Pharmacy, Chemical and Biomedical Division, Pasteur Building, City Centre Campus, Sunderland University, Sunderland, UK. fridrun.podczeck@sunderland.ac.uk
Knight
Paul
P
D001205:Ascorbic Acid / Q000737:chemistry*; D002021:Buffers; D002482:Cellulose / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004343:Drug Implants; D005069:Evaluation Studies as Topic; D006863:Hydrogen-Ion Concentration; D007052:Ibuprofen / Q000737:chemistry*; D007785:Lactose / Q000737:chemistry*; D010316:Particle Size; D011208:Powders / Q000737:chemistry; D012212:Rheology; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods*; D014867:Water / Q000737:chemistry
D002021:Buffers; D004343:Drug Implants; D011208:Powders; D014867:Water; D002482:Cellulose; D007785:Lactose; D001205:Ascorbic Acid; D007052:Ibuprofen