title: Empirical modeling of the fine particle fraction for carrier-based pulmonary delivery formulations.
abstract: In vitro study of the deposition of drug particles is commonly used during development of formulations for pulmonary delivery. The assay is demanding, complex, and depends on: properties of the drug and carrier particles, including size, surface characteristics, and shape; interactions between the drug and carrier particles and assay conditions, including flow rate, type of inhaler, and impactor. The aerodynamic properties of an aerosol are measured in vitro using impactors and in most cases are presented as the fine particle fraction, which is a mass percentage of drug particles with an aerodynamic diameter below 5 μm. In the present study, a model in the form of a mathematical equation was developed for prediction of the fine particle fraction. The feature selection was performed using the R-environment package "fscaret". The input vector was reduced from a total of 135 independent variables to 28. During the modeling stage, techniques like artificial neural networks, genetic programming, rule-based systems, and fuzzy logic systems were used. The 10-fold cross-validation technique was used to assess the generalization ability of the models created. The model obtained had good predictive ability, which was confirmed by a root-mean-square error and normalized root-mean-square error of 4.9 and 11%, respectively. Moreover, validation of the model using external experimental data was performed, and resulted in a root-mean-square error and normalized root-mean-square error of 3.8 and 8.6%, respectively.
authors: Department of Pharmaceutical Technology and Biopharmaceutics, Jagiellonian University Medical College, Kraków, Poland.
authors: Adam
authors: A
authors: Pacławski
authors: Department of Pharmaceutical Technology and Biopharmaceutics, Jagiellonian University Medical College, Kraków, Poland.
authors: Jakub
authors: J
authors: Szlęk
authors: School of Chemical and Biomedical Engineering, College of Engineering, Nanyang Technological University, Singapore.
authors: Raymond
authors: R
authors: Lau
authors: Department of Pharmaceutical Technology and Biopharmaceutics, Jagiellonian University Medical College, Kraków, Poland.
authors: Renata
authors: R
authors: Jachowicz
authors: Department of Pharmaceutical Technology and Biopharmaceutics, Jagiellonian University Medical College, Kraków, Poland.
authors: Aleksander
authors: A
authors: Mendyk
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D016208:Databases, Factual; D016503:Drug Delivery Systems; D017143:Fuzzy Logic; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008958:Models, Molecular; D008962:Models, Theoretical; D016571:Neural Networks, Computer; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism
chemical_list: D004364:Pharmaceutical Preparations
keywords: deposition modeling; empirical modeling; feature selection; fine particle fraction; genetic programming; pulmonary delivery
references: Int J Pharm. 2010 Feb 15;386(1-2):6-14
references: 19922775
references: Eur J Pharm Sci. 2010 Nov 20;41(3-4):421-9
references: 20659554
references: AAPS PharmSciTech. 2009;10(4):1252-62
references: 19866362
references: Pharm Res. 2005 Sep;22(9):1445-53
references: 16132356
references: Adv Pharm Bull. 2012;2(2):183-7
references: 24312791
references: Respir Med. 2014 Aug;108(8):1195-203
references: 24929253
references: J Pharm Sci. 2004 Nov;93(11):2681-97
references: 15389676
references: Int J Pharm. 2012 Feb 28;423(2):184-94
references: 22197772
references: Comput Biol Med. 2006 Nov;36(11):1252-67
references: 16212953
references: Int J Nanomedicine. 2013;8:4601-11
references: 24348037
references: J Microsc. 2007 Sep;227(Pt 3):254-65
references: 17760621
references: Adv Drug Deliv Rev. 2012 Mar 15;64(3):233-56
references: 21616107
references: Int J Pharm. 2010 Mar 30;388(1-2):40-51
references: 20026261
references: Drug Des Devel Ther. 2013;7:223-32
references: 23569360
references: Pharm Res. 2010 Jul;27(7):1325-36
references: 20354768
references: Adv Drug Deliv Rev. 2012 Mar 15;64(3):220-32
references: 22123598
references: Int J Pharm. 2011 Jul 15;413(1-2):93-102
references: 21540087