Hydroxypropylcellulose-flurbiprofen conjugates: design, characterization, anti-inflammatory activity and enhanced bioavailability

摘要

Herein, we report novel macromolecular prodrugs (MPDs) of flurbiprofen (FLB) onto a cellulose ether, hydroxypropylcellulose (HPC). The FLB was activated with a powerful acylation reagent carbonyldiimadazole (CDI) in N,N ′ dimethylacetamide (DMAc) solvent at room temperature. Imidazolide of FLB generated in situ reacts at 80?°C for 24?h with pre-dissolved HPC to prepare HPC-FLB conjugates. The resultant MPDs of FLB showed moderate to high degree of substitution (DS: 0.35–1.3) with good yield (70–82%). Structures were thoroughly characterized using FTIR, UV and NMR spectroscopic analyses. The pharmacokinetic studies showed that the t 1/2 and t max values of FLB from HPC-FLB conjugate were increased substantially as compare to standard FLB indicates enhanced bioavailability of drug after conjugate formation. Remarked anti-inflammatory activity of the HPC-FLB conjugate was also observed.