CELLULOSE CHEMISTRY AND TECHNOLOGY Cellulose Chem. Technol., 51 (3-4), 245-252(2017) GREEN SYNTHESIS AND ISOCONVERSIONAL THERMAL ANALYSIS OF HPMC ACETATE: A POTENT MATRIX FOR DRUG DELIVERY MUHAMMAD AMIN, * MUHAMMAD AJAZ HUSSAIN, * SYEDA AQSA BATOOL BUKHARI, * MUHAMMAD SHER * and ZAHID SHAFIQ ** * Department of Chemistry, University of Sargodha, Sargodha 40100, Pakistan ** Institute of Chemical Sciences, Bahauddin Zakariya University, Multan 60800, Pakistan Corresponding author: M. A. Hussain, majaz172@yahoo.com Received September 24, 2015 An efficient, green and commercially viable method for acetylation of cellulose ethers has been developed using acetic anhydride activated with iodine. Iodine was dissolved in acetic anhydride followed by the addition of commercially important cellulose ether, i.e., hydroxypropylmethylcellulose (HPMC) and reaction proceeded under solvent-free conditions for 3 h at 50 °C. HPMC acetates were efficiently synthesized, purified and characterized. These HPMC acetates were found soluble in different organic solvents. Under solvent-free conditions, HPMC acetate was synthesized with a DS of 2.53. Highly functionalized HPMC acetate was characterized by FTIR and 1 H NMR spectroscopic techniques. Thermal analysis and kinetics have revealed higher thermal stability imparted to HPMC after acetylation. The Flynn-Wall-Ozawa (FWO) isoconversional method was applied for kinetic studies and the energy of activation (Ea) value for HPMC acetates was found to be 71.07 kJ/mol, higher than that for unmodified HPMC. Thermodynamic parameters (H*, G* and S*) are also reported. Thermal stability was compared in terms of integral procedural decomposition temperature (IPDT) and comprehensive index of intrinsic thermal stability (ITS) using Doyle’s method. The IPDT values for HPMC and HPMC acetates were found to be 354 and 362 °C, respectively, confirming higher thermal stability of HPMC acetate as compared to HPMC. Keywords: acetylation, acetic anhydride, esterification, hydroxypropylmethylcellulose, iodine, isoconversional thermal analysis INTRODUCTION Mixed cellulose ether esters (MCEE) are famous inactive pharmaceutical ingredients in different formulations of drugs. 1 Cellulose ethers, particularly, HPMC and hydroxypropylcellulose (HPC), have enormous applications in daily life, pharmaceutical and medicinal fields. 2-4 MCEE are also of high importance in the fields of drug recrystallization 5,6 and formulation design. 7 MCEE are prepared by reacting cellulose ethers with different acetylating reagents. 8 Hence, chemical modification of HPMC to form HPMC acetates may be performed as with cellulose and HPC. 9-11 Literature has indicated a number of methods for acetylation of polysaccharides, which include the use of acetyl chloride with pyridine, 12 acetic anhydride with pyridine or 4- dimethylaminopyridine 13 and acetic anhydride activated with strong acids or metallic catalysts. 14,15 Likewise, homogeneous acetylation reactions use different solvents, which need to be removed from the product, hence require extra necessary work-up procedure. The aforesaid methods use expensive, toxic and environment- hostile reagents, hence it is necessary to develop the environment-friendly and cost-effective acetylation procedures. Iodine is environment- friendly, commercially available, cheap and powerful anhydrides activating agent. Therefore, catalytic applications of iodine for acetylation using acetic anhydride are nowadays being explored extensively on small organic molecules, 16,17 as well as on polysaccharides. 18,19 Herein, we are reporting on the isoconversional thermal analysis of commercially important and highly functionalized HPMC acetate (i.e., MCEE) and its comparison with unmodified HPMC. Our aim is to exploit the worth of an efficient and mild method that uses acetic anhydride activated with iodine.