Stability and Stabilization of Pabialgin (Cibalgin) Liquid Preparation

Abstract

Shelf-life time was supposed to be determined for active principles of original Pabialgin® (Cibalgin®) drops (allobarbital, aminophenazone) and for its stabilized liquid formulation using accelerated testing at elevated temperatures. The paper chromatography-spectrophotometric selective method was used for the determination of allobarbital and aminophenazone in presence of themselves as well as solubilisates and antioxidants. The semi-logarithmic Arrhenius equation was used to calculate shelf-life times at ambient temperature, from apparent first-order rate constants, determined at elevated temperatures. Since shelf-life times of allobarbital and aminophenazone in original pabialgin® liquid formulation were not satisfactory certain stabilization attempts were undertaken. First of all, water as a solvent was replaced with glycerol to inhibit a hydrolytic pathway of allobarbital degradation, and some antioxidants were introduced to stabilize photo-oxidation processes involved in the degradation of aminophenazone. It resulted in an unusual increase in shelf-life times of the abovementioned active principles. Aminophenazone is now replaced with propyphenazone in the so-called neo pabialgin P, because it can be transformed into a potentially cancerous nitrosamine. However, propyphenazone is also a derivative of 1-phenyl- 2,3-dimethylpyrazolone-5 similar to aminophenazone. Therefore, it should be also susceptible to oxidative processes and our findings could be used within the framework of pharmaceutical work to stabilize pabialgin P as well. A new stabilization technology of pabialgin has been successfully patented.