Stability of Benzocaine Formulated in Commercial Oral Disintegrating Tablet Platforms
- 374 Downloads
Pharmaceutical excipients contain reactive groups and impurities due to manufacturing processes that can cause decomposition of active drug compounds. The aim of this investigation was to determine if commercially available oral disintegrating tablet (ODT) platforms induce active pharmaceutical ingredient (API) degradation. Benzocaine was selected as the model API due to known degradation through ester and primary amino groups. Benzocaine was either compressed at a constant pressure, 20 kN, or at pressure necessary to produce a set hardness, i.e., where a series of tablets were produced at different compression forces until an average hardness of approximately 100 N was achieved. Tablets were then stored for 6 months under International Conference on Harmonization recommended conditions, 25°C and 60% relative humidity (RH), or under accelerated conditions, 40°C and 75% RH. Benzocaine degradation was monitored by liquid chromatography–mass spectrometry. Regardless of the ODT platform, no degradation of benzocaine was observed in tablets that were kept for 6 months at 25°C and 60% RH. After storage for 30 days under accelerated conditions, benzocaine degradation was observed in a single platform. Qualitative differences in ODT platform behavior were observed in physical appearance of the tablets after storage under different temperature and humidity conditions.
Key wordsbenzocaine degradation oral disintegrating tablet platform stability
This investigation was conducted in a facility constructed with support from Research Facilities Improvement Program Grant C06 RR15482 from the National Centre for Research Resources, NIH. This research was funded in part by Roquette America, Inc. The authors would like to thank Dr. Jerry White and Bryan Zahakaylo of UIC-RRC Mass Spectrometry Facility for significant help with LC-MS.
- 5.US FDA. Guidance for industry orally disintegrating tablets. Silver Spring, MD: Office of Pharmaceutical Science in the Center for Drug Evaluation and Research (CDER) at the Food and Drug Administration; 2008.Google Scholar
- 7.Prasad A, Langley N. The effect of secondary oxidation impurities in PVP on API stability. Tarrytown, NY: BASF CorporationGoogle Scholar
- 8.ICH. Stability testing of new drug substances and products Q1A(R2). Step 4: International Conference on the Harmonisation of Technical Requirements for Registration of Pharmaceutical for Human Use; 2003.Google Scholar
- 10.Rumbelow S, Brown JC, editors. Investigations into drug stability using LC-MS-MS data and statistical data processing. 57th American Society of Mass Spectrometry, Philadelphia, USA; 2009.Google Scholar
- 14.Crowley PJ, Martini LG. Effects of excipients on the stability of medicinal products. Chem Today. 2010;28(5 Supplement):VII–XIII.Google Scholar