Pharmaceutical formulation and in-vitro testing of Dioxy MP 14 (stabilised chlorine dioxide) against mycobacteria tuberculosis
This study was based on Dioxy MP 14 (DMP), a brand of stabilized chlorine dioxide (SCD). The active pharmaceutical ingredient (API) of DMP is chlorine dioxide (CD) which is a potent oxidant and biocide. These properties have proved invaluable for various applications. The main goals of this study were: to evaluate the effectiveness of DMP for disinfecting Mycobateria tuberculosis (TB) contaminated medical instruments, devices, floors and surfaces; to investigate the stability of DMP; and to explore possibilities for medical application of DMP. Evaluation of disinfectant activity of DMP on TB was performed using the spectrophotometric method, a modification of the European suspension test, EN 14348. M. bovis BCG was employed as surrogate in this test. Results were as follows: The minimum inhibitory concentration (MIC₉₀) = 12.5 ppm; the minimum bactericidal concentration (MBC) = 15.4 ppm; the Mycobactericidal Effect (ME) = 8.8log reduction; and the minimum inhibitory concentration (MIC₉₀) x minimum exposure time (CT) = 12.5 ppm.s. The long term stability study of DMP was performed by monitoring the rate of degradation of DMP stored in the fridge (2-8 °C), in the oven (40 °C), and under ambient conditions (15-30 °C). Analytical methods of assessing DMP concentration was by Iodometric titration method. The shelf life of DMP stored in a transparent bottle at room temperature was 9.8 weeks, as opposed to 52.7 weeks when stored in an amber colored reagent bottle at the same temperature. Both oven samples had an expiry date of about 20 weeks and the fridge samples about 70 weeks. Foam formulations for a vaginal douche (VGD), mouth rinse (MRF), and foot/sit bubble bath (F/SBB)], were developed in the laboratory. DMP and the formulated concentrate were designed to be mixed just prior to administration. During foam evaluation studies, a mechanical overhead stirrer was used to generate foam. Foamability was assessed by quantifying the amount of foam generated. The stability of foams were assessed by: 1) determining the rate of foam decay and the rate of foam drainage observed concurrently from foam loaded in a measuring cylinder; and 2) determining the life span of single bubbles of each foam system i.e. the bubble breaking time (BBT). The density of each foam system was also determined. Potentiometric acid base titration was used to select suitable adjuster alkali, and to show the benefits of employing a buffer. Concentrate development was initiated by a simple mixture of all the ingredients followed by stirring and observing the deviations from desired quality attributes of the product. The subsequent five processes were improvements designed to circumvent the shortcomings of the initial procedure to arrive at the optimized method E. Prototype formulations were employed to optimize excipient quantities to eventually arrive at an optimized master formula. In foam evaluation, it was found that sodium lauryl sulphate/ammonium lauryl sulphate/cocoamidopropyl betaine/cetostearyl alcohol (SLS/ALS/CAPB/CSA) foam system was the most appropriate to use in the formulation. NaOH was selected as the adjuster solution and KHP as the buffer. The dosage formula (DF) of the VGD and F/SBB was determined to be MDF = 5 ml of 50 ppm DMP + 5 ml concentrate + 40 ml water = 50 ml and that of MRF as MDF = 19 ml diluted concentrate + 1 ml of 50 ppm DMP. In conclusion, DMP was found to be a highly effective disinfectant against Mycobacteria. DMP has reasonable shelf life if stored appropriately. Pharmaceutical formulation from DMP was found to be delicate due to the narrow pH window of DMP stability, but is feasible.