title: In-line quantification of micronized drug and excipients in tablets by near infrared (NIR) spectroscopy: Real time monitoring of tabletting process.
abstract: The objectives of this study were to assess the utility of near infrared (NIR) spectroscopy for simultaneous in-line quantification of the contents of drug and excipients in tablets and to monitor the tabletting process in real time. Direct compression tablet formulations comprising micronized chlorpheniramine maleate, lactose, microcrystalline cellulose and magnesium stearate were used. A custom built NIR setup was used for in-line spectral acquisition (980-1900nm with 1nm resolution) during the tabletting process. Calibration models using dynamic spectral acquisition were prepared and validated using design of experiment approach. During tabletting, stratified sampling of tablets was also carried out to compare the NIR prediction results and subsequent UV analysis results for drug content. The results obtained with calibration and validation statistics confirmed the accuracy of models used to predict contents of tablet components. Stratified sampling results for drug content did not exhibit any significant statistical variation. However, in-line quantification enabled the content analysis of individual tablets in the production batch and detection of content uniformity problems towards the end of the tabletting process. Furthermore, it provided the assurance of in-process content uniformity monitoring of the individual excipients during the tabletting process.
authors.affiliation: GEA-NUS Pharmaceutical Processing Research Laboratory, Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore.
authors.forename: Atul D
authors.initials: AD
authors.lastname: Karande
authors.forename: Paul Wan Sia
authors.initials: PW
authors.lastname: Heng
authors.forename: Celine Valeria
authors.initials: CV
authors.lastname: Liew
mesh_terms: D002138:Calibration; D002482:Cellulose / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D002744:Chlorpheniramine / Q000737:chemistry*; D004339:Drug Compounding; D004867:Equipment Design; D005079:Excipients / Q000737:chemistry*; D017408:Guidelines as Topic; D007785:Lactose / Q000737:chemistry; D016018:Least-Squares Analysis; D016014:Linear Models; D025341:Principal Component Analysis; D011786:Quality Control; D015203:Reproducibility of Results; D013056:Spectrophotometry, Ultraviolet; D019265:Spectroscopy, Near-Infrared / Q000295:instrumentation / Q000592:standards; D013229:Stearic Acids / Q000737:chemistry; D013499:Surface Properties; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods* / Q000592:standards
chemical_list: D005079:Excipients; D013229:Stearic Acids; D013607:Tablets; D002744:Chlorpheniramine; C031183:stearic acid; D002482:Cellulose; D007785:Lactose; C109691:microcrystalline cellulose