Solubility of Antibiotics in Different Solvents. Part II. Non-Hydrochloride Forms of Tetracycline and Ciprofloxacin

Abstract

The aim of this work is to establish a comparison between the solubility of the hydrochloride and nonhydrochloride forms of ciprofloxacin and tetracycline in relevant solvents. For that purpose the solubilities of the non-hydrochloride forms of ciprofloxacin and tetracycline were measured in water, ethanol, 2-propanol, and acetone, in the temperature range between 293.15 and 323.15 K for ciprofloxacin and between 288.15 and 303.15 K for tetracycline. The obtained results were compared with those of part I of this study, published previously, where the solubilities of the respective hydrochloride forms of the antibiotics in the same solvents were investigated. The solubility of the hydrochloride forms in water is about 2 orders of magnitude higher than those of the respective base forms. In acetone, we see the opposite effect. For ethanol and 2-propanol the influence of the hydrochloride group of the antibiotic on the solubility in the alcohol is much smaller than for water and acetone. The experimental data was correlated with good results using two different activity coefficient models, NRTL and UNIQUAC, with UNIQUAC giving better results, particularly for ciprofloxacin. The performance of COSMO-RS model to describe the studied systems was also evaluated.

Pharmaceutical salts of ciprofloxacin with dicarboxylic acids

“…7a), which is in good agreement with the previously reported solubility data in water (0.067-0.14 mg ml À1 ) (Ross and Riley, 1990;Yu et al, 1994;Caco et al, 2008;Reddy et al, 2011;Florindo et al, 2014). DSC and XRPD analyses of the solid phase recovered after the experiment reveals transformation of CIP to its 3.7 hydrated form (Fig.…”

Two Faces of Ciprofloxacin: Investigation of Proton Transfer in Solid State Transformations

“…9 CIP is also poorly soluble in other common solvents such as ethanol, methanol, propanol, dichloromethane, acetone and chloroform. 10,11,12 The poor solubility of CIP may also be attributed to the strength of its crystal lattice, resulting in solid state-limited solubility. Intermolecular interactions, such as hydrogen bonding, Van der Waals and π−π interactions, inhibit the dissociation of drug molecules from the crystal lattice upon addition to water.…”

Synthesis, physicochemical characterization and antibacterial activity of novel (benzoylamino)methyl derivatives of quinolones

“…Considering CIPRO, it must be noticed that the experimental values for solubility in a form of hydrochloride (as used for the synthesis) are presented in Table 2. As already known, CIPRO is almost insoluble in water (0.08 mg/ml at 30 ºC) [25] and at pH 4-5 it shows the highest solubility (>40 mg/ml), but the last solubility corresponds to the hydrochloride form of CIPRO, if the pH value is adjusted with hydrochloric acid. In neutral pH, CIPRO is almost insoluble, whereas solubility increases with increasing pH value (app.…”