ABSTRACT
Extruded medicated chewing gum is a convenient but complex drug delivery system. Description of gum ingredient distribution and interactions in literature is sparse, but fundamental in product characterization and stability prediction. Although Raman spectroscopy has been used for such characterization of numerous dosage forms, its applicability to medicated chewing gum has not been studied until now. The objective was to investigate the applicability of confocal Raman imaging on chewing gum for identification and distribution of excipients and the model drug nicotine, including changes occurring during shelf life. A sample preparation protocol was composed to present an even surface of a gum cross section without altering the gum matrix texture. High-resolution Raman maps were obtained by Non Negative Least Squares (NNLS) analysis for a reference gum and gums stored for 6 months at mild (25 °C/60% RH) and accelerated (40 °C/75% RH) conditions. Additional Empty Modelling™ analysis confirmed the results of NNLS. The NNLS analysis located nicotine and the following excipients: gum base, calcium carbonate, sorbitol, xylitol, sodium carbonate, sodium bicarbonate and talc in distinct domains of the reference sample. Changes of the sample stored at accelerated conditions was discovered as sodium carbonate was not observed in this sample. Additionally, stereo light microscopy showed changes in product appearance and high-performance liquid chromatography confirmed formation of the oxidation product nicotine-1'-N-oxide in this sample. The gum formulation and its ingredients displayed characteristic Raman spectra, proving Raman imaging as a useful method for characterizing medicated chewing gums, including changes occurring during stability testing.
