Canadian Journal of Chemical Engineering, 2025 (SCI-Expanded, Scopus)
This study investigates the role of malic acid, a natural and environmentally friendly acid, in optimizing the crystallization process of amoxicillin trihydrate (AMCT). For the first time, the effects of malic acid on AMCT purity and yield were systematically analyzed and visualized using an Ishikawa diagram to elucidate complex interactions. Full factorial design and multiple response optimization were employed, with experiments conducted using Minitab V19 software. The results demonstrated that malic acid concentration, crystallization time, pH, and stirring speed significantly influence the purity and yield of AMCT crystals. The optimal conditions—2.5 M malic acid, pH 5.5, stirring speed of 1000 rpm, and crystallization time of 60 min—produced crystals with 99.21% purity and 62.6% yield. A comparative analysis with citric acid, previously studied by our group, highlighted malic acid's advantages, including improved yield and balanced purity. This research emphasizes the potential of organic acids as sustainable alternatives in pharmaceutical crystallization, offering insights into eco-friendly production methods. The findings contribute to industrial applications by promoting green chemistry principles and advancing environmentally conscious pharmaceutical practices.