Norfloxacin Cocrystals: Mechanochemical Synthesis and Scale-up Viability Through Solubility Studies

Author(s)

Ferreira, Patricia O. ; de Almeida, Amanda C. ; Costa, Giovanna de P. ; Torquetti, Carolina ; Baptista, Joao A. ; Eusebio, M. Ermelinda S. ; Caires, Flavio J. ; Castro, Ricardo A. E.

• Document type: Journal article
• Source: Journal of Pharmaceutical Sciences; v. 112, n. 8, p. 10-pg., 2023-08-01.

Abstract

Cocrystals are recognized as one of the most efficient approaches to improve aqueous solubility of Biopharmaceutical Classification System, BCS, classes II and IV drugs. Cocrystal discovery and the establishment of experimental conditions suitable for scale-up purposes are some of the main challenges in cocrystal investigation. In this work, the investigation of mechanochemical synthesis of norfloxacin cocrystals with picolinic and isonicotinic acids is performed, leading to the discovery of two new cocrystals of this important BCS class IV antibiotic, which were characterized through thermal, spectral and diffractometric analysis. Norfloxacin apparent aqueous solubility using the cocrystals is also presented, with higher values being obtained for all the investigated systems when compared to the pure drug. Norfloxacin has 3 polymorphs and several solvents/hydrates, which represents a challenge for obtaining pure cocrystal forms from solvent crystallization. This challenge was successfully overcome in this work, as experimental conditions to obtain the pure cocrystals (the new ones and also norfloxacinnicotinic acid and norfloxacin-saccharin) were established using Crystal16 equipment. This is a crucial step to envisage future scale-up procedures and therefore a valuable information for the pharmaceutical industry.& COPY; 2023 American Pharmacists Association. Published by Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 22/00239-2 - Thermodynamic and structural study of norfloxacin cocrystals
• Grantee: Giovanna de Paula Costa
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• FAPESP's process: 18/24378-6 - Synthesis, characterization and thermoanalytical study of Valsartan, Candesartan Cilexetil and Olmesartan medoxomil co-crystals
• Grantee: Flávio Junior Caires
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/07724-8 - Mechanochemical synthesis, characterization, thermoanalytical study and evaluation of the solubility of norfloxacino cocrystals
• Grantee: Giovanna de Paula Costa
• Support Opportunities: Scholarships in Brazil - Scientific Initiation