TY - JOUR
T1 - Effects of granulation process variables on the physical properties of dosage forms by combination of experimental design and principal component analysis
AU - Thapa, Prakash
AU - Choi, Du Hyung
AU - Kim, Min Soo
AU - Jeong, Seong Hoon
N1 - Publisher Copyright:
© 2018 Shenyang Pharmaceutical University
PY - 2019/5
Y1 - 2019/5
N2 - The current study was to understand how process variables of high shear wet granulations affect physical properties of granules and tablets. The knowledge gained was intended to be used for Quality-by-Design based process design and optimization. The variables were selected based on the risk assessment as impeller speed, liquid addition rate, and wet massing time. Formulation compositions were kept constant to minimize their influence on granules properties. Multiple linear regression models were built providing understanding of the impact of each variable on granule hardness, Carr's index, tablet tensile strength, surface mean diameter of granules, and compression behavior. The experimental results showed that the impact of impeller speed was more dominant compared to wet massing time and water addition rate. The results also revealed that quality of granules and tablets could be optimized by adjusting specific process variables (impeller speed 1193 rpm, water spray rate 3.7 ml/min, and wet massing time 2.84 min). Overall desirability was 0.84 suggesting that the response values were closer to the target one. The SEM image of granules showed that spherical and smooth granules produced at higher impeller speed, whereas rough and irregular shape granules at lower speed. Moreover, multivariate data analysis demonstrated that impeller speed and massing time had strong correlation with the granule and tablet properties. In overall, the combined experimental design and principal component analysis approach allowed to better understand the correlation between process variables and granules and tablet attributes.
AB - The current study was to understand how process variables of high shear wet granulations affect physical properties of granules and tablets. The knowledge gained was intended to be used for Quality-by-Design based process design and optimization. The variables were selected based on the risk assessment as impeller speed, liquid addition rate, and wet massing time. Formulation compositions were kept constant to minimize their influence on granules properties. Multiple linear regression models were built providing understanding of the impact of each variable on granule hardness, Carr's index, tablet tensile strength, surface mean diameter of granules, and compression behavior. The experimental results showed that the impact of impeller speed was more dominant compared to wet massing time and water addition rate. The results also revealed that quality of granules and tablets could be optimized by adjusting specific process variables (impeller speed 1193 rpm, water spray rate 3.7 ml/min, and wet massing time 2.84 min). Overall desirability was 0.84 suggesting that the response values were closer to the target one. The SEM image of granules showed that spherical and smooth granules produced at higher impeller speed, whereas rough and irregular shape granules at lower speed. Moreover, multivariate data analysis demonstrated that impeller speed and massing time had strong correlation with the granule and tablet properties. In overall, the combined experimental design and principal component analysis approach allowed to better understand the correlation between process variables and granules and tablet attributes.
KW - Experimental design
KW - High shear granulation
KW - Principal component analysis
KW - Process parameter
UR - http://www.scopus.com/inward/record.url?scp=85054749088&partnerID=8YFLogxK
U2 - 10.1016/j.ajps.2018.08.006
DO - 10.1016/j.ajps.2018.08.006
M3 - Article
AN - SCOPUS:85054749088
SN - 1818-0876
VL - 14
SP - 287
EP - 304
JO - Asian Journal of Pharmaceutical Sciences
JF - Asian Journal of Pharmaceutical Sciences
IS - 3
ER -