The solid dispersion has become an established solubilization technology for poorly water soluble drugs.Since a solid dispersion is basically a drug-polymer two-component system,the drug-polymer interaction is the det...The solid dispersion has become an established solubilization technology for poorly water soluble drugs.Since a solid dispersion is basically a drug-polymer two-component system,the drug-polymer interaction is the determining factor in its design and performance.In this review,we summarize our current understanding of solid dispersions both in the solid state and in dissolution,emphasizing the fundamental aspects of this important technology.展开更多
Pharmaceutical particle technology is employed to improve poor aqueous solubility of drug compounds that limits in vivo bioavailability owing to their low dissolution rate in the gastrointestinal fluids following oral...Pharmaceutical particle technology is employed to improve poor aqueous solubility of drug compounds that limits in vivo bioavailability owing to their low dissolution rate in the gastrointestinal fluids following oral administration.The particle technology involves several approaches from the conventional size reduction processes to the newer,novel particle technologies that modify the solubility properties of the drugs and produce solid,powdered form of the drugs that are readily soluble in water and can be easily formulated into various dosage forms.This review highlights the solid particle technologies available for improving solubility,dissolution and bioavailability of drugs with poor aqueous solubility.展开更多
Mesoporous silica nanoparticles(MSNs) are attracting increasing interest for potential biomedical applications. With tailored mesoporous structure, huge surface area and pore volume,selective surface functionality, as...Mesoporous silica nanoparticles(MSNs) are attracting increasing interest for potential biomedical applications. With tailored mesoporous structure, huge surface area and pore volume,selective surface functionality, as well as morphology control, MSNs exhibit high loading capacity for therapeutic agents and controlled release properties if modified with stimuli-responsive groups, polymers or proteins. In this review article, the applications of MSNs in pharmaceutics to improve drug bioavailability, reduce drug toxicity, and deliver with cellular targetability are summarized. Particularly,the exciting progress in the development of MSNs-based effective delivery systems for poorly soluble drugs, anticancer agents, and therapeutic genes are highlighted.展开更多
Solid oral controlled release formulations feature numerous clinical advantages for drug candidates with adequate solubility and dissolution rate.However,most new chemical entities exhibit poor water solubility,and he...Solid oral controlled release formulations feature numerous clinical advantages for drug candidates with adequate solubility and dissolution rate.However,most new chemical entities exhibit poor water solubility,and hence are exempt from such benefits.Although 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 form.Here,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)membrane.Compared 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 release.All-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 PVP.This 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.展开更多
The aim of this study was to improve the dissolution rate of the poorly soluble drug valsartan by delivering the drug as a liquisolid compact.Liquisolid compacts were prepared using propylene glycol as solvent,Avicel ...The aim of this study was to improve the dissolution rate of the poorly soluble drug valsartan by delivering the drug as a liquisolid compact.Liquisolid compacts were prepared using propylene glycol as solvent,Avicel PH102 as carrier,and Aerosil 200 as the coating material.The crystallinity of the newly formulated drug and the interaction between excipients was examined by X-ray powder diffraction and Fourier-transform infrared spectroscopy,respectively.The dissolution studies for the liquisolid formula-tion and the marketed product were carried out at different pH values.The results showed no change in the crystallinity of the drug and no interaction between excipients.The dissolution efficiency of valsartan at 15 min was increased from 4.02% for plain drug and 13.58% for marketed product to 29.47% for the liquisolid formulation.The increase in the dissolution rate was also found to be significant compared to the marketed product at lower pH values,simulating the gastric environment where valsartan is largely absorbed.The liquisolid technique appears to be a promising approach for improving the dissolution of poorly soluble drugs like valsartan.展开更多
基金This work was supported by the National Natural Science Foundation of China(Grant No.50873056 to Y.H.).
文摘The solid dispersion has become an established solubilization technology for poorly water soluble drugs.Since a solid dispersion is basically a drug-polymer two-component system,the drug-polymer interaction is the determining factor in its design and performance.In this review,we summarize our current understanding of solid dispersions both in the solid state and in dissolution,emphasizing the fundamental aspects of this important technology.
基金This research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education,Science and Technology(2012-0001499).
文摘Pharmaceutical particle technology is employed to improve poor aqueous solubility of drug compounds that limits in vivo bioavailability owing to their low dissolution rate in the gastrointestinal fluids following oral administration.The particle technology involves several approaches from the conventional size reduction processes to the newer,novel particle technologies that modify the solubility properties of the drugs and produce solid,powdered form of the drugs that are readily soluble in water and can be easily formulated into various dosage forms.This review highlights the solid particle technologies available for improving solubility,dissolution and bioavailability of drugs with poor aqueous solubility.
基金financial support from the National Natural Science Foundation of China (81473155)the Natural Science Fund Project of Guangdong Province (Grant No. 2016A030312013)+1 种基金the Science and Technology Plan Projects of Guangdong Province (Grant No. 2015B020232010)the Science and Technology Foundation Guangzhou (201707010103)
文摘Mesoporous silica nanoparticles(MSNs) are attracting increasing interest for potential biomedical applications. With tailored mesoporous structure, huge surface area and pore volume,selective surface functionality, as well as morphology control, MSNs exhibit high loading capacity for therapeutic agents and controlled release properties if modified with stimuli-responsive groups, polymers or proteins. In this review article, the applications of MSNs in pharmaceutics to improve drug bioavailability, reduce drug toxicity, and deliver with cellular targetability are summarized. Particularly,the exciting progress in the development of MSNs-based effective delivery systems for poorly soluble drugs, anticancer agents, and therapeutic genes are highlighted.
基金supported in part by an Ontario Research Fund-Research Excellence(ORF-RE)grant(Ontario,Canada)in partnership with Patheon by Thermo Fisher Scientific,Natural Sciences and Engineering Research Council(NSERC)of Canada Discovery Grant and Equipment Grants to Xiao Yu Wu,University of Toronto(Canada),Leslie Dan Faculty of Pharmacy Dean's Fund to Jamie Anne Lugtu-Pe,University of Toronto(Canada),Mitacs Accelerate Internship sponsored by Candoo Pharmatech Company Inc.to Xuning Zhang(Canada),NSERC CREATE ContRoL program support to Sako Mirzaie and Hao Han R.Chang(Canada),Ontario Graduate Scholarship(OGS)to Hao Han R.Chang(Canada),and Pharmaceutical Sciences graduate department scholarships to Hao Han R.Chang and Kuan Chen,University of Toronto(Canada).
文摘Solid oral controlled release formulations feature numerous clinical advantages for drug candidates with adequate solubility and dissolution rate.However,most new chemical entities exhibit poor water solubility,and hence are exempt from such benefits.Although 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 form.Here,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)membrane.Compared 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 release.All-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 PVP.This 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.
文摘The aim of this study was to improve the dissolution rate of the poorly soluble drug valsartan by delivering the drug as a liquisolid compact.Liquisolid compacts were prepared using propylene glycol as solvent,Avicel PH102 as carrier,and Aerosil 200 as the coating material.The crystallinity of the newly formulated drug and the interaction between excipients was examined by X-ray powder diffraction and Fourier-transform infrared spectroscopy,respectively.The dissolution studies for the liquisolid formula-tion and the marketed product were carried out at different pH values.The results showed no change in the crystallinity of the drug and no interaction between excipients.The dissolution efficiency of valsartan at 15 min was increased from 4.02% for plain drug and 13.58% for marketed product to 29.47% for the liquisolid formulation.The increase in the dissolution rate was also found to be significant compared to the marketed product at lower pH values,simulating the gastric environment where valsartan is largely absorbed.The liquisolid technique appears to be a promising approach for improving the dissolution of poorly soluble drugs like valsartan.
