{"title":"Microchannel-assisted crystallization of Febuxostat and its effect on crystal size: optimization by Box-Behnken design","authors":"Arunkumar M Patel, Sanjaykumar R Patel","doi":"10.1007/s12034-024-03160-0","DOIUrl":null,"url":null,"abstract":"<div><p>The aim of this research work was to investigate the impact of various process parameters on the particle size of Febuxostat (FEB) nanocrystals using response surface methodology. The continuous microchannel nanoprecipitation technique was employed to produce FEB nanoparticles with poloxamer 407 as the polymer. Initially, a Plackett-Burman design was conducted to identify the key variables that significantly influenced the nanoprecipitation process using microfluidic techniques. The independent variables considered were solvent flow rate (<i>X</i>1, ml h<sup>−1</sup>), solvent-to-antisolvent ratio (<i>X</i>2), microchannel length (<i>X</i>3, cm), drug concentration (<i>X</i>4, mg ml<sup>−1</sup>) and polymer-to-drug ratio (<i>X</i>5), while the dependent variable was the particle size (<i>Y</i>1, nm) of the nanocrystals. Among these variables, microchannel length (<i>X</i>3), drug concentration (<i>X</i>4) and polymer-to-drug ratio (<i>X</i>5) showed significant influence on the particle size of nanocrystals (<i>P</i> < 0.001). The minimum particle size observed was 303.5 ± 2.33 nm, with a polydispersity index value of 0.159 ± 0.03, achieved at a solvent-to-antisolvent ratio of 1:2, a polymer-to-drug ratio of 1:1, a microchannel length of 50 cm and a solvent flow rate of 50 ml h<sup>−1</sup>. Subsequently, a Box-Behnken design was applied to the variables identified as significant in the Plackett-Burman design, focusing on the particle size. The results indicated that microchannel length, polymer-to-drug ratio and drug concentration had a considerable impact on the particle size of FEB. Overall, the microfluidic nanoprecipitation technique demonstrated great potential as an effective technology for reducing the size of drug crystals to the nanoscale.</p></div>","PeriodicalId":502,"journal":{"name":"Bulletin of Materials Science","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bulletin of Materials Science","FirstCategoryId":"88","ListUrlMain":"https://link.springer.com/article/10.1007/s12034-024-03160-0","RegionNum":4,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MATERIALS SCIENCE, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
The aim of this research work was to investigate the impact of various process parameters on the particle size of Febuxostat (FEB) nanocrystals using response surface methodology. The continuous microchannel nanoprecipitation technique was employed to produce FEB nanoparticles with poloxamer 407 as the polymer. Initially, a Plackett-Burman design was conducted to identify the key variables that significantly influenced the nanoprecipitation process using microfluidic techniques. The independent variables considered were solvent flow rate (X1, ml h−1), solvent-to-antisolvent ratio (X2), microchannel length (X3, cm), drug concentration (X4, mg ml−1) and polymer-to-drug ratio (X5), while the dependent variable was the particle size (Y1, nm) of the nanocrystals. Among these variables, microchannel length (X3), drug concentration (X4) and polymer-to-drug ratio (X5) showed significant influence on the particle size of nanocrystals (P < 0.001). The minimum particle size observed was 303.5 ± 2.33 nm, with a polydispersity index value of 0.159 ± 0.03, achieved at a solvent-to-antisolvent ratio of 1:2, a polymer-to-drug ratio of 1:1, a microchannel length of 50 cm and a solvent flow rate of 50 ml h−1. Subsequently, a Box-Behnken design was applied to the variables identified as significant in the Plackett-Burman design, focusing on the particle size. The results indicated that microchannel length, polymer-to-drug ratio and drug concentration had a considerable impact on the particle size of FEB. Overall, the microfluidic nanoprecipitation technique demonstrated great potential as an effective technology for reducing the size of drug crystals to the nanoscale.
期刊介绍:
The Bulletin of Materials Science is a bi-monthly journal being published by the Indian Academy of Sciences in collaboration with the Materials Research Society of India and the Indian National Science Academy. The journal publishes original research articles, review articles and rapid communications in all areas of materials science. The journal also publishes from time to time important Conference Symposia/ Proceedings which are of interest to materials scientists. It has an International Advisory Editorial Board and an Editorial Committee. The Bulletin accords high importance to the quality of articles published and to keep at a minimum the processing time of papers submitted for publication.