title: A data mining approach to optimize pellets manufacturing process based on a decision tree algorithm.
abstract: The present study is focused on the thorough analysis of cause-effect relationships between pellet formulation characteristics (pellet composition as well as process parameters) and the selected quality attribute of the final product. The shape using the aspect ratio value expressed the quality of pellets. A data matrix for chemometric analysis consisted of 224 pellet formulations performed by means of eight different active pharmaceutical ingredients and several various excipients, using different extrusion/spheronization process conditions. The data set contained 14 input variables (both formulation and process variables) and one output variable (pellet aspect ratio). A tree regression algorithm consistent with the Quality by Design concept was applied to obtain deeper understanding and knowledge of formulation and process parameters affecting the final pellet sphericity. The clear interpretable set of decision rules were generated. The spehronization speed, spheronization time, number of holes and water content of extrudate have been recognized as the key factors influencing pellet aspect ratio. The most spherical pellets were achieved by using a large number of holes during extrusion, a high spheronizer speed and longer time of spheronization. The described data mining approach enhances knowledge about pelletization process and simultaneously facilitates searching for the optimal process conditions which are necessary to achieve ideal spherical pellets, resulting in good flow characteristics. This data mining approach can be taken into consideration by industrial formulation scientists to support rational decision making in the field of pellets technology.
authors.affiliation: Department of Inorganic and Analytical Chemistry, Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus University in Toruń, Jurasza 2 St., 85-089 Bydgoszcz, Poland. Electronic address: joanna.ronowicz@cm.umk.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Ronowicz
authors.affiliation: Chair of Solids Process Engineering, Faculty of Bio- and Chemical Engineering, Technical University, Dortmund, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Thommes
authors.affiliation: Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Universitätsstrasse 1, 40225 Duesseldorf, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kleinebudde
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus University in Toruń, Jurasza 2 St., 85-089 Bydgoszcz, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Krysiński
mesh_terms: D000465:Algorithms; D002626:Chemistry, Pharmaceutical; D057225:Data Mining / Q000379:methods*; D003663:Decision Trees; D004339:Drug Compounding / Q000379:methods* / Q000706:statistics & numerical data; D005079:Excipients; D010316:Particle Size
chemical_list: D005079:Excipients
keywords: Aspect ratio; Data mining; Decision trees; Pellets