Interrogating erosion-based drug liberation phenomena from hydrophilic matrices using near infrared (NIR) spectroscopy.
The present work explores the application of in situ near infrared (NIR) imaging to determine the drug release mechanisms from hydrophilic matrices containing a low solubility model drug (Compound A, with aqueous solubility at 37°C ∼0.05 mg/mL). Correlation maps generated from the NIR data determined the extent drug and HPMC co-localisation. Judicious thresholding facilitated band separation of low drug/HPMC ratio and high drug/HPMC ratio. A pseudo-image time-series confirmed the dominant erosion release mechanisms. The gel layer region showed low drug concentration with progressive dissolution. However, large drug aggregates remained unchanged even when fully "immersed" within the gel layer. From the correlation maps, further discrimination was possible for the pure drug signal, generating a highly contrasted image that enabled individual particle tracking. These contrasted images also revealed the evolution of single or clusters of drug particles. Initially, an aggregative process involving the drug particles occurred, with a subsequent migration process of such particles. This second process dominated the subsequent 90 min before significant erosion. In summary, this study has provided tentative confirmation that NIR imaging has the potential to afford insights into drug liberation phenomena where erosion is the predominant release mechanism.
Development Laboratories, MSD, Hertford Road, Hoddesdon, Hertfordshire EN11 9BU, United Kingdom. paolo_avalle@merck.com
Paolo
P
Avalle
Samuel R
SR
Pygall
Jonathan
J
Pritchard
Agnieszka
A
Jastrzemska
D002482:Cellulose / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D065347:Hypromellose Derivatives; D007785:Lactose / Q000737:chemistry; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D019265:Spectroscopy, Near-Infrared; D013229:Stearic Acids / Q000737:chemistry; D013607:Tablets; D014867:Water / Q000737:chemistry
D004364:Pharmaceutical Preparations; D013229:Stearic Acids; D013607:Tablets; D014867:Water; D065347:Hypromellose Derivatives; C031183:stearic acid; D002482:Cellulose; D008747:Methylcellulose; D007785:Lactose