Novel HPC-Ibuprofen Conjugates: Synthesis, Characterization, Thermal Analysis and Degradation Kinetics.

Naturally occurring hydrophilic polysaccharides are nowadays attracting the vigil eye of researchers working in areas of drug design and development. Amongst them, hydrophilic biopolymer hydroxypropylcellulose (HPC) is of particular interest. Its unique geometry allows the attachment of drug molecules with higher covalent loading as the hydroxyls are projected outside the polymer chains. The HPC-Ibuprofen conjugates as macromolecular prodrugs were therefore synthesized employing homogenous and one pot reaction methodology using p-toluenesulfonyl chloride. Present strategy appeared effective to synthesize conjugates with high yield (77-81%). Acid-base titration after saponification and 1H-NMR spectroscopic analyses have revealed high degree of drug substitution (DS 0.88-1.40) on to HPC. Uni-modal absorptions were observed in gel permeation chromatograms which indicated no significant degradation of polymer. Macromolecular prodrugs with different DS of ibuprofen were synthesized, purified, characterized and found soluble in organic solvents. From thermogravimetric analysis, initial, maximum and final degradation temperatures of the conjugates were calculated and compared for relative thermal stability. Thermal degradation kinetics was also studied and results have indicated that degradation of conjugates follows about first order kinetics as calculated by Kissinger model. The energy of activation was also found moderate 92.38, 99.34 and 87.34 kJ/mol as calculated using Friedman, Broido and Chang models. It was found that these novel prodrugs of ibuprofen were thermally stable therefore these may have potential pharmaceutical applications. [ABSTRACT FROM AUTHOR]