Optimization of melt pelletization in a high shear mixer.
The effects of process conditions and binder content on the process yield and pellet characteristics of two formulations prepared by melt pelletization in a laboratory-type high shear mixer were investigated. The formulations were prepared using Gelucire 50/13 and Lutrol F68 as meltable binders. The factors under investigation were impeller speed, mixing time, mixer load, binder concentration, and their reciprocal interactions. Analysis of variance (ANOVA) was used in order to study the significance of above mentioned process variables on the useful yield. Twenty-seven experiments were required for the response surface methodology based on Box-Behnken experimental design (24 combinations with three replications of the centre point) for each formulation. The control over the process and the quality of the resulting pellets were found to depend on the rheological properties of the binders used. In the case of a low viscosity binder (Gelucire 50/13), the process was easily controllable whereas in the case of a high viscosity binder (Lutrol F68), the process was more difficult to control. The useful yield of the formulation in the case of the low viscosity binder was found to be mostly influenced by the concentration of the binder. On the other hand, different binder concentrations did not affect the useful yield of the formulation prepared by use of the high viscosity binder. In the latter case, mixing time was identified as the variable that mostly influenced the pelletization process. Finally response surface methodology was applied to find the optimum values of the process variables.
Bukovec
P
P
KRKA d.d., Novo mesto, Smarjeska cesta 6, 8501 Novo mesto, Slovenia. polona.bukovec@krka.biz
Kroselj
V
V
Turk
S
S
Vrecer
F
F
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000737:chemistry; D000704:Analysis of Variance; D002152:Calorimetry, Differential Scanning; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods*; D005079:Excipients / Q000737:chemistry; D005223:Fats / Q000737:chemistry; D006358:Hot Temperature; D064747:Lansoprazole; D008274:Magnesium / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D009821:Oils / Q000737:chemistry; D010316:Particle Size; D044367:Phase Transition; D011092:Polyethylene Glycols / Q000737:chemistry; D011786:Quality Control; D012212:Rheology / Q000379:methods; D012995:Solubility; D013499:Surface Properties; D013607:Tablets / Q000737:chemistry*; D013997:Time Factors; D044366:Transition Temperature; D014783:Viscosity
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D004337:Drug Carriers; D005079:Excipients; D005223:Fats; C506200:Lutrol; D009821:Oils; D013607:Tablets; C005479:magnesium carbonate; D064747:Lansoprazole; C071184:Gelucire 50-13; D011092:Polyethylene Glycols; D008274:Magnesium