A Comprehensive Study of a New 1.75 Hydrate of Ciprofloxacin Salicylate: SCXRD Structure Determination, Solid Characterization, Water Stability, Solubility, and Dissolution Study

Abstract

One problem that often arises during the formulation of a dosage form is the solubility and dissolution of the active ingredients. This problem arises in ciprofloxacin, which is a BCS class IV fluoroquinolone antibiotic. A pseudopolymorph is a kind of polymorph in which the number of hydrates is different. In this study, a new pseudopolymorph comprised of ciprofloxacin and salicylic acid was found, namely the salt ciprofloxacin salicylate 1.75 hydrate form. This new solid phase was analyzed by Fourier-transform infrared spectroscope (FTIR), Raman spectroscopy, and thermal analysis and proven by Powder X-ray Diffractometry (PXRD) analysis. The crystal structure was successfully determined by Single Crystal X-ray Diffractometry (SCXRD) analysis. It was found that the piperazinyl group of ciprofloxacin is protonated by H+ from the carboxylic group of salicylic acid. In the unit cell, two ciprofloxacin and two salicylic acid molecules were independent with four water molecules, in which one water molecule had 0.5 occupancy due to inversion symmetry. Interestingly, this hydrate crystal dehydrated by grinding for 105 minutes forms an anhydrous crystalline phase, which was analyzed with FTIR, Raman spectroscopy, thermal analysis, and PXRD. The solubility and dissolution tests were carried out using UV-Visible spectrophotometry and a multiple linear regression method. This new hydrate solid phase has a better profile than the original ciprofloxacin crystal, according to the solubility and dissolution tests.

Electrochemical Sensor Based on a Composite of Reduced Graphene Oxide and Molecularly Imprinted Copolymer of Polyaniline–Poly(o-phenylenediamine) for Ciprofloxacin Determination: Fabrication, Characterization, and Performance Evaluation

“…Notably, the copolymer pattern was shifted from its initial position, and other small peaks were observed. The shift can be attributed to the presence of CIP in the copolymer matrix . For the post-elution MIP/rGO, signals from the rGO pattern overlapped with the copolymer, resulting in only one broad peak at 15.1°.…”

Levofloxacin Cocrystal/Salt with Phthalimide and Caffeic Acid as Promising Solid-State Approach to Improve Antimicrobial Efficiency

“…Melting point data of physical mixtures with different mole ratios were plotted against melting temperature, as shown in Supplementary Figures S1 and S2 . The “W” shape binary phase diagrams of LEV with PTH and CFA indicate that 1:1 molar ratio leads the formation of cocrystal/salt [ 58 , 59 , 60 , 61 ]. Additionally, the melting point of respective pure materials, LEV-PTH cocrystal and LEV-CFA salt are presented in Table 1 .…”

New Organic Salt from Levofloxacin-Citric Acid: What Is the Impact on the Stability and Antibiotic Potency?

“…Generally, antibiotics have poor stability [ 6 ], i.e., ciprofloxacin, a fluoroquinolone antibiotic, can be improved by chemical derivatization or solid-state development. Recently, we composed and reported ciprofloxacin salicylate, 1.75 hydrates, that modulated the solubility [ 7 ]. However, the development of fluoroquinolone antibiotics has generated some derivates, including levofloxacin (LF), which exhibits a broader spectrum of antibacterial activity [ 8 ] and better physicochemical properties.…”