Development & Optimization of Anti-Dandruff Shampoo by Modifying its Rheological Behavior

Abstract

Pharmaceutical product stability is an important issue in pharmaceutical industry. The rheological behavior of a pharmaceutical product affects its stability and performance characteristics such as, foaming properties and filling process during production. Ketoconazole, imidazole antifungal agent, is a weak base with two pKa-values 6.15 and 2.94. It is unstable in aqueous medium and vulnerable to degradation if not properly formulated. Oxidation and hydrolysis are the most degradation routes affecting its stability. The aim of this study to assess the effect of formulation factors such as, pH, the amount of the rheology modifier, rheological behavior and temperature on the stability of ketoconazole in aqueous media. Different formulations of 2 gm% ketoconazole were prepared, using different percent concentrations of the rheology modifier (NaCl) as 0.8 gm%, 0.2 gm%, 0.4 gm%, 0.1 gm% at different pH values 5.5, 6.5 and 7.5. Experimental formulations were prepared at different temperature and time intervals. The measurements of pH and viscosity of the prepared shampoo were evaluated during stability. Stability studies were carried out as per ICH guidelines for 18 months and monitored by validated stability indicating HPLC method (linearity: 60-140 μg/mL; R2=0.9995; acceptable accuracy and precision %RSD < 1.0%). The rheological behavior of the system possess a yield point (minimum shear stress for flow to commence) and time dependency. A reduction in viscosity occurs on shearing with time and rebuilding of viscosity on standing. The key is the rate at which the structure is rebuilt. This is a function of the nature of the thixotropic agent, its concentration in the vehicle or medium, and the amount of agitation before use. The prepared ketoconazole shampoo was high stable at high pH (6.5-7.5) and at temperature < 30 °C during the manufacturing process. Furthermore, the amount of rheology modifier had a high significant effect on the stability of ketoconazole. Formulations containing 0.1 gm% NaCl showed better stability and exhibited ideal thixotropic rheological behavior. The rheology of dispersed systems is among the most important of their physical properties, which influences not only the physical stability of the systems, but often also profoundly affects the performance features, their quality, and their utility. In dealing with rheological parameters, and in case of thixotropic systems, long shearing times should be avoided. Temperature changes can also produce spurious results, since shear stress at a constant shear rate, is also a function of temperature. It is important to consider the optimum pH for the product, since the properties of the product, particularly rheology, can be quite dependent on the pH of the system. In conclusion, the expected shelf life of the final ketoconazole formulation was stable for 18 months.