Kinetic study the stability of vitamin C in liquid multivitamin formulations

Abstract

To formulate an oral liquid multivitamin preparation, the stability testing program was designed to assess the stability of vitamin C in the presence of various pharmaceutical aids. The influence of vehicles, antioxidants, chelating agents, suspending agents, flavor, preservatives, pH and buffers on both chemical and physical stability of the products were thoroughly investigated. It was found that vitamin C was stabilized when either of sorbitol, glycerin, propylene glycol, corn syrup or water was used as vehicle while syrup USP and sodium metabisulfite accelerated its degradation. In the pH range 2.5 – 4 studied, the degradation was decreased when pH was lowered and citrate buffer had more browning effect than acetate buffer. Other agents such as suspending agents, flavor preservatives showed no significant effect on vitamin C degradation. Based on these preformulation studies, five formulations of liquid multivitamins were developed and evaluated according to accelerated stability testing techniques at 40˚, 50˚, 60˚, 70℃ and room temperature storage. The degradation of Vitamin C in all formulations were found to be a first-order. A linear regression line was obtained from Arrhenius plot of the reaction rates against reciprocal of degree kelvin ( 1/T ) in every product. The heat of activations falled in the range 13-18 kcal/mol in all formulations. The predicted degradation rate obtained from Arrhenius plots were found to be essentially equal to the values obtained from actual room temperature storage. Therefore, accelerated stability testing method is suitable for prediction of product’s shelf-life. All of formulations developed have the actual degradation rates (k) in the range 1.96 x 10⁻³ to 3.28 x 10⁻³ day-1 and the predicted rates in the range 2.34x 10⁻³ to 3.15 x 10⁻³ day⁻¹ at room temperature which are all better stabilized than a marketed product with similar active components ( k = 5.43 x 10⁻³ day⁻¹). The best formulated product was stabilized about 2 times of the commercial one. However, an overage of 30% of the labeled amount was required to obtain a shelf-life of about 150 days product. Moreover, construction of graph to provide simple means for prediction of product shelf-life were made according to chemical kinetic principles by plotting shelf-life (t₉₀) against reciprocal of degree kelvin ( 1/T ). This technique is very useful and handy for rapid and accurate prediction of product shelf –life at any temperature.