Paper AS+BI-MoA5
TOF-SIMS Cluster Beam Depth Profiling and 3D Imaging of Oral Drug Delivery Films

Monday, October 30, 2017, 3:00 pm, Room 13

Dissolvable oral thin film (OTF) drug delivery systems are gaining increased interest as convenient alternatives to more conventional tablets and capsules for drug delivery applications. The OTF’s are typically made by mixing an active pharmaceutical ingredient (API) into a dissolvable polymer that is administered to the patient by placing under the tongue or against the inside of the cheek. Direct adsorption of the API into the systemic circulation bypasses gastrointestinal delivery and can provide higher levels of bioavailability and a more rapid release profile in appropriate medications. One critical challenge with further development of OTF drug delivery systems is the lack of appropriate measurement tools for the characterization of API concentration, phase and dose uniformity throughout the depth of the polymer film (typically ~100 um in thickness). Furthermore, OTF’s are currently manufactured as bulk sheets with fixed levels of API. This is a significant roadblock to realization of OTF’s for personalized medicine where there is a growing interest in manufacturing of OTF’s with individualized and patient-specific API dosages. One promising method of production of such films that is currently being explored in our laboratory is the used of drop on demand inkjet printing to precisely deposit individualized API doses onto prefabricated films.

In this work, we explore the utility of Time of Flight Secondary Ion Mass Spectrometry (TOF-SIMS) using gaseous cluster ion beam (GCIB) depth profiling for the characterization of the lateral and in-depth distribution of API’s in model OTF films. Three types of films were examined; (1) model thin films of pullulan, (2) model thin films of pullulan that had been dosed using drop on demand inkjet printing with various concentrations of relevant API’s and (3), commercially available OTF films (single and multilayer films) containing the anti-opioid medications buprenorphine and naloxone which are widely used medications for treatment of opioid dependency. Cluster SIMS depth profiling was able to resolve compositional differences throughout the depth of each of these films (>70 um in thickness) and localize the individual API’s. Furthermore, the ability to characterize the lateral and in depth distribution of API’s in individual inkjet droplets will be demonstrated as well as the use of inkjet printing to prepare in situ concentration standards for evaluation of dosage variability. Finally, we also demonstrate the use THz Raman imaging for chemical identification of the API and possible phase changes due to the use of inkjet-printed formulations.