title: Characterization of tablet film coatings using a laser-induced breakdown spectroscopic technique.
abstract: Laser-induced breakdown spectroscopy (LIBS) was evaluated as an early phase process analytical technology (PAT) tool for the rapid characterization of pharmaceutical tablet coatings. Measurement of coating thickness, uniformity, and photodegradation-predictive potential of the technique were evaluated. Model formulation tablets were coated with varying amounts (2%-4% wt/wt) of red and yellow Opadry II, and a pulsed laser was used to sample at multiple sites across the tablet face. LIBS was able to successfully detect the emissions of Fe and Ti in the coated samples, and a proportional increase in signal with coating thickness was observed. Batch-to-batch variability in the coating procedure was also easily monitored by LIBS. The coating thickness was non-uniform across the tablet surface with higher thickness at the edges, likely due to the concave shape of the tablet. Film coating levels and color of the film had been subjected to photostability studies according to the International Conference on Harmonisation (ICH) guideline to determine effectiveness of the film coats. LIBS measurements of coating thickness provided a good correlation (R (2) > 0.99) to photodegradation as measured by high-performance liquid chromatography (HPLC). Last, the concentration of Fe in the coating was varied and monitored by LIBS. Increasing photostability was observed with increasing levels of ferric oxide, providing a new understanding of the photoprotection mechanism in the coated formulation. Determination of levels of ferric oxide and coating thickness by LIBS demonstrated its utility as a good PAT tool for the determination of photoprotection of the drug, thereby enabling facile optimization of the coating process.
authors.affiliation: Merck Frosst Canada Ltd, Pharmaceutical Research and Development, 16711 TransCanada Highway, Kirkland, QC, Canada.
authors.forename: M Cecilia
authors.initials: MC
authors.lastname: Madamba
authors.forename: Wayne M
authors.initials: WM
authors.lastname: Mullett
authors.forename: Smita
authors.initials: S
authors.lastname: Debnath
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kwong
mesh_terms: D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004396:Coloring Agents / Q000737:chemistry* / Q000528:radiation effects; D004339:Drug Compounding; D004355:Drug Stability; D004867:Equipment Design; D005079:Excipients / Q000737:chemistry; D005240:Feasibility Studies; D005290:Ferric Compounds / Q000737:chemistry; D007834:Lasers; D008027:Light; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000528:radiation effects; D010777:Photochemistry; D013057:Spectrum Analysis / Q000295:instrumentation; D013499:Surface Properties; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods*
chemical_list: D004396:Coloring Agents; D005079:Excipients; D005290:Ferric Compounds; D004364:Pharmaceutical Preparations; D013607:Tablets; C000499:ferric oxide