NIR chemical imaging to guide/support BMS-561389 tablet formulation development.
The objective of this study was to determine whether the particle size of extra-granular tartaric acid affects the uniformity of its distribution within BMS-561389 tablets. A near-infrared imaging technique was used to assess the distribution of tartaric acid near the surface of tablet tops and bottoms. Three batches of BMS-561389 tablets were manufactured using three lots of granular tartaric acid having different particle size distributions. Near-Infrared chemical images were acquired on the tops and bottoms of 15 tablets from each lot. Spectra were collected from 1350 to 1600 nm in 10 nm increments and 16 co-added scans at each wavelength. Data were analyzed using ISys 3.1 (Spectral Dimensions, Inc.) Chemical Imaging Software. Data analysis consisted of preprocessing, principal component analysis, and image analysis of the principal component scores image. It was feasible to map tartaric acid particles near the surface of BMS-561389 tablets using near infrared chemical imaging. The tartaric acid particle size statistics based on image analysis results correlated well with pre-compaction measurements using a laser-light scattering method. The image analysis results indicate that segregation of tartaric acid between tablet tops and bottoms was apparent in tablets lots containing both the largest and intermediate-size tartaric acid particles. For tablets made with the smallest tartaric acid particles, differences between tablet tops and bottoms in either the number of tartaric acid particles or the percent tablet surface area covered by tartaric acid were not statistically different at the 95% confidence level.
Hilden
L R
LR
Bristol-Myers Squibb Co, New Brunswick, NJ 08903-0191, USA. Hilden_Lori_R@lilly.com
Pommier
C J
CJ
Badawy
S I F
SI
Friedman
Emil M
EM
D000990:Antithrombin III / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D005079:Excipients; D007555:Isoxazoles / Q000737:chemistry*; D010316:Particle Size; D011720:Pyrazoles / Q000737:chemistry*; D019265:Spectroscopy, Near-Infrared; D013607:Tablets; D013644:Tartrates / Q000737:chemistry; D013678:Technology, Pharmaceutical
D005079:Excipients; D007555:Isoxazoles; D011720:Pyrazoles; D013607:Tablets; D013644:Tartrates; C500057:razaxaban; D000990:Antithrombin III; C029768:tartaric acid