Solid oral controlled release formulations feature numerous clinical advantages for drug candidates with adequate solubility and dissolution ***,most new chemical entities exhibit poor water solubility,and hence are e...
详细信息
Solid oral controlled release formulations feature numerous clinical advantages for drug candidates with adequate solubility and dissolution ***,most new chemical entities exhibit poor water solubility,and hence are exempt from such *** combining drug amorphization with controlled release formulation is promising to elevate drug solubility,like other supersaturating systems,the problem of drug recrystallization has yet to be resolved,particularly within the dosage ***,we explored the potential of an emerging,non-leachable terpolymer nanoparticle(TPN)pore former as an internal recrystallization inhibitor within controlled release amorphous solid dispersion(CRASD)beads comprising a poorly soluble drug(celecoxib)reservoir and insoluble polymer(ethylcellulose)*** to conventional pore former,polyvinylpyrrolidone(PVP),TPN-containing membranes exhibited superior structural integrity,less crystal formation at the CRASD bead surface,and greater extent of celecoxib ***-atom molecular dynamics analyses revealed that in the presence of TPN,intra-molecular bonding,crystal formation tendency,diffusion coefficient,and molecular flexibility of celecoxib were reduced,while intermolecular H-bonding was increased as compared to *** work suggests that selection of a pore former that promotes prolonged molecular separation within a nanoporous controlled release membrane structure may serve as an effective strategy to enhance amorphicity preservation inside CRASD.
暂无评论