Ciprofloxacin is a second-generation fluoroquinolone antibiotic widely used in the treatment of Gram-negative and selected Gram-positive bacterial infections. It has global clinical importance and inclusion in the World Health Organisation Model List of Essential Medicines. Ciprofloxacin continues to be manufactured extensively as a generic active pharmaceutical ingredient (API). The development of efficient, scalable, and impurity-controlled synthetic routes remains a major focus in pharmaceutical process chemistry. This review provides a comprehensive comparative analysis of reported synthetic methodologies for ciprofloxacin, encompassing classical batch processes, modified Gould–Jacobs strategies, nucleophilic aromatic substitution pathways, boron-chelate-mediated synthesis, solid-phase approaches, and modern continuous-flow techniques. Each route is critically evaluated with respect to key reaction steps, operational conditions, yield, purity, scalability, and environmental impact. Comparative assessment highlights the advantages and limitations of traditional multistep syntheses versus emerging streamlined and flow-based processes. Recent continuous manufacturing strategies demonstrate improved efficiency, reduced reaction times, and enhanced sustainability compared with conventional batch methods. Overall, this review aims to provide an integrated perspective to guide rational route selection, process optimisation, and future development of greener and economically viable ciprofloxacin API manufacturing.
Sudipta Santra, Pradipta Bera, Mouly Mitra, Rounak Bhattacharya, Rituraj Kumar Dutta* (Sun,) studied this question.