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

Muhammad Ajaz Hussain; Iqra Shad; Iram Malik; Fasiha Amjad; Tehreem Kausar; Kamran; Muhammad Sher; Muhammad Nawaz Tahir; Nisar Ullah; Muhammad Ashraf; Syed Nasir Abbas Bukhari

doi:10.1016/j.jsps.2020.06.009

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

Saudi Pharm J. 2020 Jul;28(7):869-875. doi: 10.1016/j.jsps.2020.06.009. Epub 2020 Jun 23.

Affiliations

¹ Department of Chemistry, University of Sargodha, Sargodha 40100, Pakistan.
² College of Pharmacy, University of Sargodha, Sargodha 40100, Pakistan.
³ Chemistry Department, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi Arabia.
⁴ Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Aljouf, Sakaka 2014, Saudi Arabia.

Abstract

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.

Keywords: Anti-inflammatory activity; Flurbiprofen; Hydroxypropylcellulose; Pharmacokinetics; Prodrug.