Effects of oily drug rheology on content uniformity in granules obtained by wet granulation with a high-shear mixer.
The purpose of the present work was to elucidate the effects of viscosity on the content uniformity of an oily drug in granules obtained by wet granulation with a high-shear mixer. For this purpose, we used d-alpha-tocopheryl acetate diluted with a medium chain fatty acid triglyceride having viscosities in the range from 26.0 to 726.0 mPas. It was found that independent of viscosity, nuclei rich in the oily drug were formed in the process of mixing with powder and that those nuclei prevented uniform distribution of the drug throughout the granules. To achieve content uniformity, it is necessary for the nuclei formed before granulation to be fragmented and for the oily drug to be distributed uniformly throughout granules. Tensile strength of the nuclei was attributed to the viscosity of the oily drug, according to a model for tensile strength of a granule under dynamic conditions. When viscosity of the oily drug increased, tensile strength of the nuclei increased and the extent of the drug demixing in granules was large and constant independent of granulation time. On the other hand, when viscosity of the oily drug decreased, tensile strength of the nuclei decreased. The extent of the drug demixing was small with lower viscosity but increased with a prolonged granulation time. In the case of the oily drug, we found that a decrease in its viscosity led to the improvement of the content uniformity in granules. The viscosity of the oily drug significantly affects its content uniformity in granules by a high-shear mixer granulation.
Formulation Research Laboratories, Kawashima Research, Eisai Co., Ltd., Hashima, Gifu, Japan. y3-kato@hhc.eisai.co.jp
Yoshiteru
Y
Kato
Toshihiko
T
Namiki
Masao
M
Kawamura
D004339:Drug Compounding / Q000295:instrumentation*; D009821:Oils / Q000737:chemistry*; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011208:Powders; D011786:Quality Control; D012212:Rheology; D033081:Shear Strength; D013696:Temperature; D024505:Tocopherols; D014280:Triglycerides / Q000737:chemistry; D014783:Viscosity; D014867:Water / Q000737:chemistry; D024502:alpha-Tocopherol / Q000031:analogs & derivatives* / Q000737:chemistry
D009821:Oils; D004364:Pharmaceutical Preparations; D011208:Powders; D014280:Triglycerides; D014867:Water; D024502:alpha-Tocopherol; D024505:Tocopherols