Development of microparticles coated with poly-γ-glutamic acid to improve oral absorption of a poorly water-soluble drug.

Novel microparticles coated with poly-γ-glutamic acid (PGA) were developed to improve the oral absorption of indomethacin (IM), a poorly water-soluble drug. Microparticles containing γ-IM (IMbulk-PGA) or crystal polymorph α-IM (IMpolymorph-PGA) were prepared. Additionally, microparticles were prepared containing α-IM without PGA (IMpolymorph without PGA). IMbulk-PGA and IMpolymorph-PGA exhibited better drug retention properties on mucin disks. Drug release rates from IMpolymorph-PGA and IMpolymorph without PGA were higher than from IM bulk powder, and drug release from IMbulk-PGA was also improved. Drug release from IMbulk-PGA could be improved with the use of Tween 80. In addition, PGA may influence the ionization of IM or affect specific molecular interactions. After the microparticles were administered orally to mice, IMbulk-PGA and IMpolymorph-PGA increased the plasma drug concentration more rapidly compared with IM bulk powder, but IMpolymorph without PGA did not increase the plasma drug concentration. It was considered that IMbulk-PGA and IMpolymorph-PGA rapidly reached the intestinal membrane through the mucus layer and IM was absorbed quickly. Because IMbulk-PGA and IMpolymorph-PGA showed a rapid increase in plasma drug concentration, IMbulk-PGA and IMpolymorph-PGA could be useful preparations to improve the gastrointestinal absorption of IM. Furthermore, IMbulk-PGA may maintain higher plasma drug concentrations than IMpolymorph-PGA.