A top-down spectroscopic approach for correlating coating thickness distributions with the dissolution profiles of enterically coated pellets.

Pharmaceutical dosage forms such as tablets and capsules are often coated with a functional polymer to modify the drug release. To obtain the drug release profiles, ensure quality control and predict in-vivo performance, dissolution studies are performed. However, dissolution tests are time-consuming, sample destructive and do not readily allow for at-line or in-line characterization. Rapid assessment of functional coatings is essential for products where a single capsule is comprised of hundreds of functionally-coated pellets and the collective drug release kinetics of the entire capsule depends on contributions from each pellet. Here, single Raman measurements were used to evaluate the coating thickness distributions of a dosage form comprised of small, functionally-coated pellets in capsules. First, the composition and physicochemical properties of pellets were characterized by multivariate analysis assisted Raman mapping of pellet cross-sections. Second, a method of collecting single Raman spectrum with spectral contributions from the coating and API layers was developed and optimized to estimate the thickness of coatings. The coating thicknesses obtained from single Raman measurements of pellets in each capsule revealed thickness distributions that correlated with the dissolution profiles (capsules with one distribution had single stage release and capsules with two distributions had a two-stage release). Finally, an unsupervised multivariate analysis method was demonstrated as a rapid and efficient way to correlate dissolution profiles of enterically coated pellets. In summary, this study presents a non-destructive and rapid characterization method for assessing coating thickness and has the potential to be applied in process analytical technologies to ensure coating uniformity and predict product dissolution rate performance.

In Situ Grown Gold Nanoisland-Based Chemiresistive Electronic Nose for Sniffing Distinct Odor Fingerprints.

Chemiresistors based on metal-insulator-metal structures are attractive transducers for rapid tracing of a wide repertoire of (bio)chemical species in the vapor phase. However, current fabrication techniques suffer greatly from sensor-to-sensor variability, limiting their reproducible and reliable application in real-world settings. We demonstrate a novel, facile, and ubiquitously applicable strategy for fabricating highly reliable and reproducible organothiol-functionalized gold nanoisland-based chemiresistors. The novel fabrication technique involves iterative in situ seeding, growth, and surface functionalization of gold nanoislands on an interdigitated electrode, which in turn generates a multi-layered densely packed continuous gold nanoisland film. The chemiresistors fabricated using the proposed strategy exhibited high sensor-to-sensor reproducibility owing to the controlled iterative seeding and growth-based fabrication technique, long-term stability, and specificity for detection and identification of a wide variety of volatile organic compounds. Upon exposure to a specific odor, the chemiresistor ensemble comprised nine different chemical functionalities and produced a unique and discernable odor fingerprint that is reproducible for at least up to 90 days. Integrating these odor fingerprints with a simple linear classifier was found to be sufficient for discriminating between all six odors used in this study. We believe that the fabrication strategy presented here, which is agnostic to chemical functionality, enables fabrication of highly reliable and reproducible sensing elements, and thereby an adaptable electronic nose for a wide variety of real-world gas sensing applications.