title: In-line ATR-UV and Raman Spectroscopy for Monitoring API Dissolution Process During Liquid-Filled Soft-Gelatin Capsule Manufacturing.
abstract: Complete dissolution of the active pharmaceutical ingredient (API) is critical in the manufacturing of liquid-filled soft-gelatin capsules (SGC). Attenuated total reflectance UV spectroscopy (ATR-UV) and Raman spectroscopy have been investigated for in-line monitoring of API dissolution during manufacturing of an SGC product. Calibration models have been developed with both techniques for in-line determination of API potency. Performance of both techniques was evaluated and compared. The ATR-UV methodology was found to be able to monitor the dissolution process and determine the endpoint, but was sensitive to temperature variations. The Raman technique was also capable of effectively monitoring the process and was more robust to the temperature variation and process perturbations by using an excipient peak for internal correction. Different data preprocessing methodologies were explored in an attempt to improve method performance.
authors.affiliation: Analytical and Bioanalytical Development, Bristol-Myers Squibb Co., 1 Squibb Drive, New Brunswick, New Jersey, 08901, USA. boyong.wan@bms.com.
authors.forename: Boyong
authors.initials: B
authors.lastname: Wan
authors.affiliation: Analytical and Bioanalytical Development, Bristol-Myers Squibb Co., 1 Squibb Drive, New Brunswick, New Jersey, 08901, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Zordan
authors.affiliation: Analytical and Bioanalytical Development, Bristol-Myers Squibb Co., 1 Squibb Drive, New Brunswick, New Jersey, 08901, USA.
authors.forename: Xujin
authors.initials: X
authors.lastname: Lu
authors.affiliation: Analytical and Bioanalytical Development, Bristol-Myers Squibb Co., 1 Squibb Drive, New Brunswick, New Jersey, 08901, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: McGeorge
mesh_terms: D002138:Calibration; D002214:Capsules / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D005079:Excipients / Q000737:chemistry; D005780:Gelatin / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012995:Solubility; D013059:Spectrum Analysis, Raman / Q000379:methods; D013678:Technology, Pharmaceutical / Q000379:methods*; D013696:Temperature; D014466:Ultraviolet Rays
chemical_list: D002214:Capsules; D005079:Excipients; D004364:Pharmaceutical Preparations; D005780:Gelatin
keywords: ATR-UV; Raman; in-line monitoring; soft-gelatin capsule