Compatibility of chewing gum excipients with the amino acid L-cysteine and stability of the active substance in directly compressed chewing gum formulation.
Using L-cysteine chewing gum to eliminate carcinogenic acetaldehyde in the mouth during smoking has recently been introduced. Besides its efficacy, optimal properties of the gum include stability of the formulation. However, only a limited number of studies exist on the compatibility of chewing gum excipients and stability of gum formulations. In this study we used the solid-state stability method, Fourier transform infrared spectroscopy and isothermal microcalorimetry to investigate the interactions between L-cysteine (as a free base or as a salt) and excipients commonly used in gum. These excipients include xylitol, sorbitol, magnesium stearate, Pharmagum S, Every T Toco and Smily 2 Toco. The influence of temperature and relative humidity during a three-month storage period on gum formulation was also studied. Cysteine alone was stable at 25 degrees C/60% RH and 45 degrees C/75% RH whether stored in open or closed glass ambers. As a component of binary mixtures, cysteine base remained stable at lower temperature and humidity but the salt form was incompatible with all the studied excipients. The results obtained with the different methods corresponded with each other. At high temperature and humidity, excipient incompatibility with both forms of cysteine was obvious. Such sensitivity to heat and humidity during storage was also seen in studies on gum formulations. It was also found that cysteine is sensitive to high pressure and increase in temperature induced by compression. The results suggest that the final product should be well protected from temperature and humidity and, for example, cooling process before compression should be considered.
Kartal
Alma
A
Faculty of Pharmacy, Division of Biopharmaceutics and Pharmacokinetics, University of Helsinki, PO Box 56, Helsinki 00014, Finland. alma.kartal@helsinki.fi
Björkqvist
Mikko
M
Lehto
Vesa-Pekka
VP
Juppo
Anne Mari
AM
Marvola
Martti
M
Sivén
Mia
M
D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000737:chemistry*; D002151:Calorimetry; D002638:Chewing Gum; D003545:Cysteine / Q000008:administration & dosage / Q000737:chemistry*; D004344:Drug Incompatibility; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients / Q000737:chemistry*; D006813:Humidity; D011312:Pressure; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature
D016588:Anticarcinogenic Agents; D002638:Chewing Gum; D005079:Excipients; D003545:Cysteine