Multifaceted approaches for enhanced bioavailability of poorly water-soluble drugs via microneedle and nanoparticle systems

Abstract

This study aimed to improve the bioavailability of poorly water-soluble drugs through multifaceted approaches with microneedle and nanoparticle delivery systems. We developed crystalline (flurbiprofen/PVP = 1:0.03, weight ratio) and amorphous (flurbiprofen/PVP = 1:2.5, weight ratio) microneedle systems through a vacuum-based method to improve the transdermal drug delivery of flurbiprofen, a poorly water-soluble drug. In addition, nanoparticle (celecoxib/ copovidone/SLS/meglumine = 1:1:0.2:0.02, weight ratio) and solid self-nanoemulsifying granule system (S-SNEGS, celecoxib/Captex®355/Tween 80®/TPGS/Ca-silicate/Avicel® PH 101 = 3.5:25:60:15:50:100, weight ratio) were prepared using a spray dryer and a fluid bed granulator to improve the oral drug delivery of the poorly water-soluble drug celecoxib, respectively. The developed microneedle systems showed different release profiles and physicochemical properties depending on the crystallinity of the drug in the microneedle system. The drug was released as a sustained-release profile in the crystalline microneedle system, whereas it was released as a fast-dissolving profile in the amorphous microneedle system. The developed microneedle systems showed significantly improved solubility and release compared to pure drug powder. In particular, the amorphous microneedle system showed fast-dissolving profiles and high bioavailability (approximately 2-fold and 9-fold, respectively) compared to the crystalline microneedle systems and needleless flurbiprofen-loaded film. Therefore, amorphous microneedle systems are recommended as transdermal drug delivery systems for flurbiprofen. Next, the developed nanoparticles had different solubility, dissolution and physicochemical properties depending on the microenvironment pH of the nanoparticle system. Among them, the solubility (approximately 166,000-fold) and oral bioavailability (approximately 4-fold) of the pH-modified nanoparticles showed the most significant improvement compared to celecoxib powder. In addition, the solubility, dissolution rate and oral bioavailability of the developed solid self-nanoemulsifying drug delivery systems were evaluated. S-SNEGS showed the most significant improvement in solubility (approximately 241,000-fold) and oral bioavailability (approximately 5-fold) compared to pure drug powder. Therefore, the pH-modified nanoparticle and the S-SEGS systems are recommended as nanoparticle drug delivery systems for celecoxib.