betadex and chloroacetic-acid

This study aims to synthesize, characterize and investigate the water solubility and cytotoxicity of branched anionic/cationic β-cyclodextrins (bβCDs) obtained by reaction with epichlorohydrin and chloroacetic acid or choline chloride, respectively, by a single step polycondensation reaction. Obtained ionic bβCDs were investigated as an attempt to comparatively study anionic and cationic bβCDs. Water solubility of both ionic derivatives was similar (400 mg/mL) at neutral and basic pHs and remarkably higher than that of their neutral homologues. Additionally, a pH-dependent solubility of anionic bβCDs was observed. Cytotoxicity of ionic bβCDs was evaluated on Human colon carcinoma Caco-2 cells and high cell viability (>99%) was observed in the range of 0-100 mg/mL for anionic and cationic samples, in the same range of that of neutral and parent β-CDs. Additionally, complexes formation capacity with triclosan, a poor water soluble antimicrobial agent, was confirmed by several techniques observing a complexation limit around 4 mg/mL for both systems and higher stability constant for anionic bβCDs than cationic derivatives.

Topics: Acetates; Anti-Infective Agents, Local; beta-Cyclodextrins; Caco-2 Cells; Cell Survival; Drug Carriers; Epichlorohydrin; Humans; Ions; Solubility; Triclosan; Water

Hydroxypropyl beta-cyclodextrin (HP beta CyD) has been shown to stabilize a wide variety of chemically distinct pharmaceutical entities through inclusion-complex formation between drug and cyclodextrin. The effect of HP beta CyD on the acid-catalysed hydrolysis of benzylpenicillin (penicillin G) was evaluated in chloroacetate buffer at pH 2.20. At penicillin G: cyclodextrin molar concentration ratios from 1:1 to 1:10, HP beta CyD effected stabilization of penicillin G by 1.56- to 5.21-fold. At all temperatures, the observed first-order rate constant (kobs) values assumed a non-linear, Michaelis-Menten type decrease as a function of increasing HP beta CyD concentration. Degradation of penicillin G complexed with HP beta CyD (penicillin G-HP beta CyD), was approximately ninefold slower than uncomplexed penicillin G. The proportion of penicillin G degrading in either of these forms was, in turn, determined by the equilibrium constant for the complexation. The apparent thermodynamic and activation parameters for the complexation between penicillin G and HP beta CyD have also been evaluated. The negative standard enthalpy change (delta H degrees) for the complexation implied that the penicillin G-HP beta CyD complex would be predisposed towards enhanced stability, and thus the kobs value for the hydrolysis of penicillin G decreased with reduction of temperature in these systems. The lack of difference between the enthalpies of activation (delta H ++) for the hydrolysis of uncomplexed and complexed penicillin G seemed to be compensated by the significant difference between the entropies of activation (delta S ++) for these hydrolytic reactions. The results indicate that HP beta CyD represents a viable means of stabilization of penicillin G solutions at the pH employed in this study.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Acetates; beta-Cyclodextrins; Buffers; Cyclodextrins; Drug Stability; Penicillin G; Thermodynamics