Acta Pharm. 50 (2000) 219-228
The stability of 0.5% (m/V) thiamine hydrochloride solution in different vehicles containing sucrose (40%, m/V), dextrose (21.1%, m/V), fructose (21.1%, m/V, each) or dextrose-fructose mixture (21.1%, m/V each) was studied at room temperature (25 ± 0.5 °C) and at the elevated temperatures (45, 55 and 65 ± 0.5 °C).
The stability studies were followed in McIlvaine's citric-phosphate buffer system at pH 3.5. The concentration of the drug was determined according to the USP HPLC method. The results obtained proved that thiamine hydrochloride was unstable in the presence of sucrose; the drug loss in presence of sucrose has been attributed to the monosaccharides formed by decomposition of sucrose solutions. Drug stability examined in the presence of each of the decomposition products of sucrose, fructose and dextrose revealed significant drug loss, the extent depending on the type of the sugar, temperature and time of storage.
Thiamine degradation followed first-order kinetics at all temperatures examined. An Arrhenius plot was used to calculate the shelf-life of drug preparations at 25 °C.
The in vitro stability of the drug from syrups aged at 55 °C and at room temperature was studied. The data obtained showed drug availability was impaired in stored syrups possibly due to the formation of irreversible drug-sugar condensation products.
A trial was made to overcome the problem resulting from drug-sugar interactions. A sugar-free vehicle was suggested consisting of 30% (m/V) sorbitol. Compared to the stability of the drug in 40% (m/V) sucrose, the suggested formulation showed improved stability, in the estimated shelf-life of 41.4 months compared to 6.9 months for the sucrose-containing formulation.
Keywords: thiamine hydrochloride, stability, sucrose, sorbitol, dextrose, fructose, liquid dosage form