Investigating the Role of Citric Acid as a Natural Acid on the Crystallization of Amoxicillin Trihydrate

[Image: see text] This study investigates the use of environmentally friendly citric acid as the main player in the process, rather than as an additive, to remove impurities from amoxicillin trihydrate (AMCT) crystals, aiming to optimize their purity and yield. By manipulating the concentration of citric acid, mixing speed, crystallization time, and pH, the researchers conducted experiments using a full factorial design. The dissolution stage was analyzed in both batch and continuous crystallization processes, emphasizing the significance of citric acid in enhancing crystallization. HPLC analyses were performed on the resulting crystals, and the data were analyzed using the Multi-Vari Chart program. The findings demonstrated that higher citric acid concentrations positively affected the yield, while factors such as crystallization time, mixing speed, and pH also contributed to the increased yield. The crystals obtained exhibited desirable dimensions sought after in the pharmaceutical industry, eliminating the need for additional purification steps. This study showcased the potential of citric acid in AMCT crystallization, offering advantages in product design, purification, and synthesis. The optimized conditions included a citric acid concentration of 2.0 M, mixing speed of 1000 rpm, crystallization time of 120 min, and pH of 5.5. Notably, the developed process proved to be environmentally friendly by avoiding the use of harmful chemicals, serving as a green alternative for crystallization processes, and producing purer AMCT products. Overall, this research contributes to the existing literature by highlighting the efficacy of citric acid in impurity removal and the optimization of AMCT crystal purity and yield.