Using experimental design to optimize the process parameters in fluidized bed granulation on a semi-full scale

被引:77
作者
Rambali, B
Baert, L
Massart, DL
机构
[1] Free Univ Brussels, Farmaceut Inst, B-1090 Brussels, Belgium
[2] Janssen Res Fdn, B-2340 Beerse, Belgium
关键词
granulation process; granule properties; fluid bed; central composite design; optimization; regression model;
D O I
10.1016/S0378-5173(01)00658-5
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
A face-centered central composite design was applied in order to optimize the granulation process on a semi-full scale (30-kg batch) for the geometric mean granule size. The granulation process variables investigated were: inlet air temperature, inlet airflow rate, spray rate and inlet air humidity. Based on the process variables, the theoretical powder bed moisture content after the spraying process and a measure for the droplet size were determined. Multiple regression modeling was used to develop two models for the granule size: an empirical model, based on the four process parameters. and a fundamental model, based on the balance between the granule growth affected by the theoretical powder bed moisture content and the droplet size and the breakage effect of the airflow rate. These regression models were used to optimize the granulation process to obtain a granule size between 300 and 500 mum. Additional experiments confirmed that these models were valid. Other granule properties, namely the geometric standard deviation, the Hausner index. the angle of repose and the moisture content, were evaluated at the optimal operation conditions. (C) 2001 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:149 / 160
页数:12
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