Pharmaceutical manufacturing process improvement with quality focus and effect of api particle size on the finish product dissolution rate

One of the most prominent features of our age is that sustainability and continuous change waves affect almost everything. In order to adapt to their environment with these waves of change and gain competitive advantage in this direction, it is important for enterprises to be renewed at the necessary levels, to improve their processes and to offer high quality products to the market at the most cost-effective way. When the critical parameters in the processes are taken under control, it is known that in efficient processes are reduced by achieving more stable processes, and that unnecessary waste can be prevented by rejecting the non-conforming products due to these reasons. The "dissolution" parameter, which is defined as solubility and dissolution rate, is a very important process parameter in terms of drug efficacy. When the parameters affecting the solubility and dissolution rate are listed, it is reported that organic molecules with high molecular size are less soluble in water than small molecules and generally decrease in solubility with increasing molecular weight. By using these informations a solid form, active substances named " moxifloxacin" used and tested. The effect of particle size difference of the same active substance from different raw material suppliers on finished product quality was investigated in a product of film tablet form produced using moxifloxacin active substance. The data were statistically analyzed and supported by case studies. As a result, it has been determined that the optimum particle size distribution of the drug production processes and the product dissolution rate is optimal. The functions and the effects of the critical raw materials in the unit formula, which affect the quality of the finished product, were determined and the parameters required to be optimized in the process were determined by evaluating the existing data. In the process optimization, the effect of the action taken in the production process on the finished product specifications was examined. The effectiveness of the data obtained after statistical optimization using control parameters such as Cp, Cpk was measured and supported by case studies. As a result, the optimum operating range of the drug substance distribution of the active substance to the improvement of drug production processes and the rate of dissolution of the product was determined as the size value corresponding to the cumulative size distribution representing the size of the particles where 10%, 50%, and 90% of the sample remained. These values are d10>10, d50>50, d90>100. Amount of water used in the granulation step was increased, granular torque value was kept in the range of 250-300 N, the sieve type and the speed of the shredder was increased and process was optimized. Keywords: Continuous improvement, critical process control parameters, high quality production in the pharmaceutical industry, particle size distribution, quality by design (QbD), process optimisation.