Multiple cross-linked hydroxypropylcellulose-succinate-salicylate: Prodrug design, characterization, stimuli responsive swelling-deswelling and sustained drug release

A hydroxypropylcellulose-succinic anhydride (HPC-SAn) conjugate was synthesized homogeneously at 80 °C for 6 h under N₂ in N,N-dimethylacetamide (DMA). The HPC-SAn conjugate was further covalently linked with salicylic acid (SA) drug using the versatile reagent ZrOCl₂·8H₂O at 80 °C for 6 h. Multiple crosslinking of the benign HPC-SAn-SA conjugate was achieved using oxalyl chloride. The resultant cross-linked prodrug (CL-HPC-SAn-SA conjugate) was characterized using different spectroscopic techniques. UV/Vis analysis of the HPC-SAn-SA conjugate has indicated that it contains 26 mg of SA per 100 mg. CL-HPC-SAn-SA showed reasonably good swelling properties in water and at different physiological pH values (6.8 and 7.4). However, negligible swelling was observed at acidic pH (1.2). Kinetic studies revealed that CL-HPC-SAn-SA followed second order swelling kinetics. Additionally, the CL-HPC-SAn-SA conjugate showed stimuli responsive (pH 7.4/1.2) swelling-deswelling properties. The effect of different pH values (1-10) on the swelling of CL-HPC-SAn-SA was also studied. Thermal analysis revealed that the cross-linked prodrug CL-HPC-SAn-SA was thermally more stable compared to pure SA. This method of multiple crosslinking of drugs with polysaccharides and the resultant prodrugs has a high potential for pharmaceutical and medicinal applications.