Increasing the degree of supersaturation of drugs and maintaining their proper stability are very important in improving the oral bioavailability of poorly soluble drugs by a supersaturated drug delivery system(SDDS)....Increasing the degree of supersaturation of drugs and maintaining their proper stability are very important in improving the oral bioavailability of poorly soluble drugs by a supersaturated drug delivery system(SDDS). In this study, we reported a complex system of Soluplus–Copovidone(Soluplus–PVPVA)loaded with the model drug silybin(SLB) that could not only maintain the stability of a supersaturated solution but also effectively promote oral absorption. The antiprecipitation effect of the polymers on SLB was observed using the solvent-shift method. In addition, the effects of the polymers on absorption were detected by cellular uptake and transport experiments. The mechanisms by which the Soluplus–PVPVA complex promotes oral absorption were explored by dynamic light scattering, transmission electron microscopy, fluorescence spectra and isothermal titration calorimetry analyses. Furthermore, a pharmacokinetic study in rats was used to demonstrate the advantages of the Soluplus–PVPVA complex. The results showed that Soluplus and PVPVA spontaneously formed complexes in aqueous solution via the adsorption of PVPVA on the hydrophilichydrophobic interface of the Soluplus micelle, and the Soluplus–PVPVA complex significantly increased the absorption of SLB. In conclusion, the Soluplus–PVPVA complex is a potential SDDS for improving the bioavailability of hydrophobic drugs.展开更多
Solid dispersion is one of the most promising strategies to improve oral bioavailability of poorly soluble API.However,there are inconsistent dissolution performances of solid dispersion reported which entails further...Solid dispersion is one of the most promising strategies to improve oral bioavailability of poorly soluble API.However,there are inconsistent dissolution performances of solid dispersion reported which entails further investigation.In this study,solid dispersions of ketoprofen in three hydrophilic carriers,i.e.PVP K30,PVPVA 6:4 and PVA were prepared and characterized.Physical characterization of the physical mixture of ketoprofen and carriers shows certain extent of amorphization of the API.This result is coinciding to evaluation of drug-polymer interaction using ATR-FTIR whereby higher amorphization was seen in samples with higher drug-polymer interaction.XRPD scanning confirms that fully amorphous solid dispersion was obtained for SD KTP PVP K30 and PVPVA system whereas partially crystalline system was obtained for SD KTP PVA.Interestingly,dissolution profiles of the solid dispersion had shown that degree of amorphization of KTP was not directly proportional to the dissolution rate enhancement of the solid dispersion system.Thus,it is concluded that complete amorphization does not guarantee dissolution enhancement of an amorphous solid dispersion system.展开更多
基金supported by the National Natural Science Foundation of China (grant Nos. 81573378 and 81773651)the Shanghai Science and Technology Innovation Action Plan for Basic Research, China (No. 17430741500)
文摘Increasing the degree of supersaturation of drugs and maintaining their proper stability are very important in improving the oral bioavailability of poorly soluble drugs by a supersaturated drug delivery system(SDDS). In this study, we reported a complex system of Soluplus–Copovidone(Soluplus–PVPVA)loaded with the model drug silybin(SLB) that could not only maintain the stability of a supersaturated solution but also effectively promote oral absorption. The antiprecipitation effect of the polymers on SLB was observed using the solvent-shift method. In addition, the effects of the polymers on absorption were detected by cellular uptake and transport experiments. The mechanisms by which the Soluplus–PVPVA complex promotes oral absorption were explored by dynamic light scattering, transmission electron microscopy, fluorescence spectra and isothermal titration calorimetry analyses. Furthermore, a pharmacokinetic study in rats was used to demonstrate the advantages of the Soluplus–PVPVA complex. The results showed that Soluplus and PVPVA spontaneously formed complexes in aqueous solution via the adsorption of PVPVA on the hydrophilichydrophobic interface of the Soluplus micelle, and the Soluplus–PVPVA complex significantly increased the absorption of SLB. In conclusion, the Soluplus–PVPVA complex is a potential SDDS for improving the bioavailability of hydrophobic drugs.
基金the financial support received from the short term grant 304/PFARMASI/6313055,Universiti Sains Malaysia in carrying out this work.
文摘Solid dispersion is one of the most promising strategies to improve oral bioavailability of poorly soluble API.However,there are inconsistent dissolution performances of solid dispersion reported which entails further investigation.In this study,solid dispersions of ketoprofen in three hydrophilic carriers,i.e.PVP K30,PVPVA 6:4 and PVA were prepared and characterized.Physical characterization of the physical mixture of ketoprofen and carriers shows certain extent of amorphization of the API.This result is coinciding to evaluation of drug-polymer interaction using ATR-FTIR whereby higher amorphization was seen in samples with higher drug-polymer interaction.XRPD scanning confirms that fully amorphous solid dispersion was obtained for SD KTP PVP K30 and PVPVA system whereas partially crystalline system was obtained for SD KTP PVA.Interestingly,dissolution profiles of the solid dispersion had shown that degree of amorphization of KTP was not directly proportional to the dissolution rate enhancement of the solid dispersion system.Thus,it is concluded that complete amorphization does not guarantee dissolution enhancement of an amorphous solid dispersion system.
