title: Controlling the chemical stability of a moisture-sensitive drug product through monitoring and identification of coating process microenvironment.
abstract: The objective of this work was to monitor and identify the impact of coating microenvironment, as measured by PyroButtons(®) data loggers, on the chemical stability of a moisture-sensitive drug molecule brivanib alaninate (BA). BA tablets were coated at two different scales (15 and 24 in pan). PyroButtons(®) data loggers were allowed to move freely within the tablet bed to record the temperature and relative humidity conditions of the tablet bed. The tablet moisture content at the end of the coating runs, and the rate of hydrolysis of the BA tablets based on HPLC analysis was found to be a function of the coating thermodynamic microenvironment. Wetter coating conditions resulted in tablets with higher water content and showed greater degradation upon storage. The coating process which yielded acceptable stability in a 15 in coater was transferred to a 24 in coater by maintaining similar tablet-bed relative humidity and temperature conditions. This was compared to a traditional scale-up approach where the environmental equivalency factor (EEF) was matched between scales during coating. The moisture content observed across the two scales indicated that maintaining a similar tablet-bed microenvironment ensured consistent results between scales.
authors.affiliation: Drug Product Science and Technology, Bristol-Myers Squibb Co. One Squibb Drive, New Brunswick, NJ 08903, United States. Electronic address: umesh.kestur@bms.com.
authors.forename: Umesh
authors.initials: U
authors.lastname: Kestur
authors.affiliation: Drug Product Science and Technology, Bristol-Myers Squibb Co. One Squibb Drive, New Brunswick, NJ 08903, United States.
authors.forename: Preetanshu
authors.initials: P
authors.lastname: Pandey
authors.affiliation: Drug Product Science and Technology, Bristol-Myers Squibb Co. One Squibb Drive, New Brunswick, NJ 08903, United States.
authors.forename: Sherif
authors.initials: S
authors.lastname: Badawy
authors.affiliation: Analytical and Bioanalytical Development, Bristol-Myers Squibb Co. One Squibb Drive, New Brunswick, NJ 08903, United States.
authors.forename: Judy
authors.initials: J
authors.lastname: Lin
authors.affiliation: Drug Product Science and Technology, Bristol-Myers Squibb Co. One Squibb Drive, New Brunswick, NJ 08903, United States.
authors.forename: Divyakant
authors.initials: D
authors.lastname: Desai
mesh_terms: D000409:Alanine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D004356:Drug Storage; D006813:Humidity; D006868:Hydrolysis; D013607:Tablets; D013696:Temperature; D013816:Thermodynamics; D014227:Triazines / Q000008:administration & dosage / Q000737:chemistry; D014867:Water / Q000737:chemistry*
chemical_list: D013607:Tablets; D014227:Triazines; D014867:Water; C509922:brivanib; D000409:Alanine
keywords: Chemical stability; Coating; Microenvironment; PyroButtons; Thermodynamics; Water-activity