Screening of high shear mixer melt granulation process variables using an asymmetrical factorial design.
The effects of process conditions on the granulometric characteristics of a placebo formulation prepared in a 10 l high shear mixer by single-step melt granulation were studied. The factors under investigation were: binder grade, mixer load, presence of the deflector (all of analysed at two levels), binder concentration, impeller speed, massing time, type of impeller blades (these four at three levels) and jacket temperature (considered at four levels). Two granule characteristics were analysed: the geometric mean diameter and the percentage of particles finer than 315 microm. In order to screen simultaneously the above-mentioned factor levels, an asymmetrical factorial design was adopted, which allowed the reduction in the number of runs from 2592 to 25. Additionally, this technique permitted the selection of the factor levels which have the major 'weight' on the two granule characteristics under study. Two additional trials were performed to attest the screening validity.
Voinovich
D
D
Department of Pharmaceutical Sciences, University of Trieste, Piazzale Europa 1, I-34127, Trieste, Italy. vojnovic@univ.trieste.it
Campisi
B
B
Moneghini
M
M
Vincenzi
C
C
Phan-Tan-Luu
R
R
D002626:Chemistry, Pharmaceutical / Q000295:instrumentation / Q000379:methods*; D004339:Drug Compounding; D065347:Hypromellose Derivatives; D007785:Lactose / Q000737:chemistry; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D015999:Multivariate Analysis; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011208:Powders; D012107:Research Design
D011208:Powders; D065347:Hypromellose Derivatives; D011092:Polyethylene Glycols; D008747:Methylcellulose; D007785:Lactose