Thermo-sensitive microparticles of poly(N-isopropylacrylamide) grafted ethylcellulose by the spray drying method

Abstract

The thermo-sensitive microparticles were prepared by the spray drying method. Ethylcellulose-g-PNIPAM was synthesized by the graft copolymerization of PNIPAM onto ethylcellulose using ammonium persulphate as radical initiator in chloroform/DMSO (50/50) ml mixed solvent system. The ethylcellulose-g-PNIPAM was characterized with various techniques such as FTIR spectroscopy, NMR spectroscopy and DSC measurements. The degree of graft polymerization (DGP) which means the length of a PNIPAM grafts was calculated by the $^{13}$C NMR spectra with an assumption that the number of PNIPAM grafts (NG) is 1. Microparticles were prepared by the spray drying method using B-191 Mini Spray Dryer. Three samples with different graft length of PNIPAM were used as the polymer and allopurinol was used as a model drug. The morphology of microparticles was studied using scanning electron microscopy(SEM). The particle size distribution of microparticles was narrow. The release rate of allopurinol from ECGPN8 microparticles was slower at 40℃(above the LCST) than that of 25℃(below the LCST) probably due to the collapse of PNIPAM chains by temperature, while ECGPN4 microparticles didn``t. The thermo-sensitive release behavior of microparticles was affected by the length of a PNIPAM grafts. A relatively large burst effect was found at the start of release and attributed to the disadvantage of the spray drying method; the rapid solvent evaporation in the spray chamber of a spray dryer results in the free drug. The graft copolymer ethylcellulose-g-PNIPAM could be used as a component of temperature-sensitive devices in various forms and the spray drying method provides an efficient and rapid tool for the preparation of microparticles except the large burst effect.