TY - JOUR
T1 - Characterization of Powder- and Tablet Properties of Different Direct Compaction Grades of Mannitol Using a Kohonen Self-organizing Map and a Lasso Regression Model
AU - Kosugi, Atsushi
AU - Leong, Kok Hoong
AU - Tsuji, Hinako
AU - Hayashi, Yoshihiro
AU - Kumada, Shungo
AU - Okada, Kotaro
AU - Onuki, Yoshinori
N1 - Funding Information:
Conflicts of interest: The authors declare no conflict of interest. The Laboratory of Pharmaceutical Technology, University of Toyama is an endowed department, supported by an unrestricted grant from the Nichi-Iko Pharmaceutical Co. Ltd. (Toyama, Japan).
Publisher Copyright:
© 2020 American Pharmacists Association®
PY - 2020/8
Y1 - 2020/8
N2 - The purpose of this study was to accumulate enhanced technical knowledge about the powder properties of direct compaction grades of mannitol that could lead to new tablet formulations. Fifteen different commercial direct compaction grades of mannitol were tested. Ten different powder properties representing flowability, particle size, specific surface area and manufacturing properties were measured. In addition, model tablets of each mannitol grade were prepared, and their disintegration time, friability, and tensile strength were measured. The data were analyzed by principle component analysis and a Kohonen self-organizing map to find correlations between powder properties. Self-organizing map clustering successfully classified the test grades into 5 distinct clusters having different powder properties. Each cluster was well characterized by statistical profiling. Subsequently, the contribution of the powder properties to the tablet properties was investigated by a least absolute shrinkage- and selection operator (Lasso) regression model. Mannitol grades with a larger particle size (D90) were prone to produce tablets with longer disintegration time, while a larger specific surface area of the particles was positively associated with tablets with higher mechanical strength. Our findings provide valuable information for the design of tablet formulations.
AB - The purpose of this study was to accumulate enhanced technical knowledge about the powder properties of direct compaction grades of mannitol that could lead to new tablet formulations. Fifteen different commercial direct compaction grades of mannitol were tested. Ten different powder properties representing flowability, particle size, specific surface area and manufacturing properties were measured. In addition, model tablets of each mannitol grade were prepared, and their disintegration time, friability, and tensile strength were measured. The data were analyzed by principle component analysis and a Kohonen self-organizing map to find correlations between powder properties. Self-organizing map clustering successfully classified the test grades into 5 distinct clusters having different powder properties. Each cluster was well characterized by statistical profiling. Subsequently, the contribution of the powder properties to the tablet properties was investigated by a least absolute shrinkage- and selection operator (Lasso) regression model. Mannitol grades with a larger particle size (D90) were prone to produce tablets with longer disintegration time, while a larger specific surface area of the particles was positively associated with tablets with higher mechanical strength. Our findings provide valuable information for the design of tablet formulations.
UR - http://www.scopus.com/inward/record.url?scp=85086110539&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85086110539&partnerID=8YFLogxK
U2 - 10.1016/j.xphs.2020.05.010
DO - 10.1016/j.xphs.2020.05.010
M3 - Article
C2 - 32473211
AN - SCOPUS:85086110539
VL - 109
SP - 2585
EP - 2593
JO - Journal of Pharmaceutical Sciences
JF - Journal of Pharmaceutical Sciences
SN - 0022-3549
IS - 8
ER -