Improved Drug Loading and Sustained Release of Entecavir‐loaded PLGA Microsphere Prepared by Spray Drying Technique

Abstract

The purpose of this study was to construct a poly(lactic‐co‐glycolic acid) microparticle (PLGA MP) of entecavir (ETV), an anti‐viral agent for hepatitis B, for parenteral sustained delivery. To improve entrapment efficiency of the hydrophilic small compound in MPs, different fabrication methods such as double emulsion solvent evaporation and spray‐drying method were investigated. The prepared MPs were highly spherical, and the surface was smooth, irrespective of fabrication methods. On the other hand, the drug loading efficiency and in vitro release profile of ETV from the MPs were largely depending on fabrication methods. When the MPs were prepared by double emulsion method, the drug loading efficiency was extremely low (< 16.2%), with rapid drug release within two hours. On the other hand, the MPs prepared by spray‐drying process after dissolving the hydrophilic drug and PLGA polymer in acetic acid exhibited high loading efficiency more than 95%, with prolonged release profile more than 25 days. The drug release profile from the MPs prepared by spray‐drying technique was effectively adjusted by varying the lactide/glycolide ratio (75/25 or 50/50) or terminal group (carboxylic acid or ester terminated) of the biodegradable polymers. Therefore, the novel SR system fabricated by spray drying technique is expected to be an advantageous tool for the management of chronic hepatitis B with less frequent drug administration and improved patient's adherence.