PHYSICO-CHEMICAL AND ANTIMICROBIAL EVALUA TIONS OF CIPROFLOXACIN AND MOXIFLOXACINE CONJUGATES OF CHITOSAN AND POLYETHYLENE GLYCOL POLYMERS

Abstract

Objective: The objective of the project was to study the physico-chemical characteristics of the chitosan and polyethylene glycol polymer conjugates of ciprofloxacin and moxifloxacin. In spite of the strong activities of these drugs the experiment was to evaluate their activities in conjugated forms and to assess whether this will confer any special advantage. Methodology: The conjugates were prepared by esterification reactions. The drug-to carrier ratios were determined. The ester conjugates were characterised by melting point, UV, IR, solubility in different solvent systems after which they were subjected to stability tests (hydrolysis) in different buffers systems. Halflives were also estimated. Microbiological evaluations of the conjugates were determined. Results: Evidence for ester formation was observed from the physicochemical changes indicated below. The UV absorption maxima for pure ciprofloxacin, moxifloxacin, chitosan and polyethylene glycol were 270 nm; 295 nm; 260 nm, 240 nm respectively while ciprofloxacin-chitosan and moxifloxacin-chitosan, ciprofloxacin- PEG and moxifloxacin-PEG were 300 nm, 270 nm, 280 nm and 300 nm respectively. The drug - to- carrier ratios were found to be: Cipro - Chitosan; 1.0 : 5.1; Moxi- Chitosan, 1.0 : 4.7; Cipro - PEG. 1.0 - 1.1 and Moxi - PEG, 1.0: 1.05. The infrared spectra showed characteristic absorption bands in the carbonyl region (1700cm-1 and 1800 cm-1 ). The melting points for ciprofloxacin-chitosan, moxiflolxacin-chitosan, ciprofloxacin-PEG and moxifloxacin-PEG were 245- 248oC; 270 - 275oC; 280-283oC and 290-293oC respectively. All the conjugates were insoluble in ethanol, diethyl ether, n-hexane and acetone but soluble or sparingly soluble in water, methanol, and glacial acetic acid, hydrochloric and sulphuric acids. Hydrolysis constants for all the conjugates showed linearity for between 0 and 8 hours and flexes into a plateau at 10 hours in phosphate buffered solutions of pH 6.1, pH 7.4 and pH 8.1. Corresponding regression equations were generated. The rates of hydrolysis of all the conjugates at pH 6.1 varied from 1.73 to 9.04 x 10-2 s -1 ; at pH 7.4 the rate varied from 1.47 to 8.54 x 10-2 s -1 and at pH 8.1 the rate varied from 2.85 to 9.60 x 10-2 .s-1 The corresponding half-lives of hydrolysis varied from 5.1 to 40.8 hours; at pH 7.4 the halflife varied from 8.1 to 47.0 hours and at pH 8.1 the half-life varied from 7.2 to 24.3 hours. Antimicrobial activities of the conjugates against Staph. aureus, Staph. pneumonia, E.coli, Salmonella typhi and Pseu. aeroginosa. showed enhanced sensitivity of between 40 and 50%.