Effect of crystallization behavior of polyethylene glycol 6000 on the properties of granules prepared by fluidized hot-melt granulation (FHMG).
The objective of this study was to investigate the effect of the crystallization behavior of Macrogol 6000 (polyethylene glycol 6000; PEG 6000), used as a binder, during the solidification process on the properties of mononucleic granules prepared by the fluidized hot-melt granulation (FHMG) technique. Crystallization of PEG 6000 from molten liquid was investigated using differential scanning calorimetry (DSC) and hot stage microscopy. The results obtained from the measurement of isothermal crystallization demonstrated that crystallization of PEG 6000 was either slow or rapid. Analysis based on solid-state decomposition showed that slow crystallization was due to the two-dimensional growth of nuclei mechanism, while rapid crystallization was due to the three-dimensional growth of nuclei mechanism. Observation of the crystallization of PEG 6000 by hot stage microscopy supported the existence of two different crystallization mechanisms. Granules containing PEG 6000 that underwent rapid crystallization during FHMG showed a significantly higher fraction powder under 150 microm in diameter. This was caused by the loss of powder particles from the surface of mononucleic granules during the solidification process, because many cracks were observed after crystallization of PEG 6000 with a short isothermal crystallization time (ICT) due to the reduced of sticking of particles. The results of this study suggested that the crystallization behavior of the binder during the solidification process of FHMG can influence the properties of the resultant granules, such as particle size distribution, content uniformity or taste masking. It was also indicated that measuring the ICT using DSC was a useful method to classify PEG 6000.
Shizuoka Pharmaceutical Research Center, Pharmaceutical Technology Research Laboratories, Daiichi Pharmaceutical Co., Ltd., Kanaya-cho, Japan. kidokknl@daiichipharm.co.jp
Motonori
M
Kidokoro
Kaoru
K
Sasaki
Yasuo
Y
Haramiishi
Norio
N
Matahira
D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D005079:Excipients / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008855:Microscopy, Electron, Scanning; D008970:Molecular Weight; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011208:Powders; D013696:Temperature; D014783:Viscosity
D005079:Excipients; D011208:Powders; D011092:Polyethylene Glycols