The aim of this study was to improve the in vitro dissolution rate and oral bioavailability of oleanolic acid(OA), a water insoluble drug belonging to BCS class IV. Hot melt extrusion(HME) was applied to develop OA am...The aim of this study was to improve the in vitro dissolution rate and oral bioavailability of oleanolic acid(OA), a water insoluble drug belonging to BCS class IV. Hot melt extrusion(HME) was applied to develop OA amorphous solid dispersions. The characterizations of the optimal formulation were performed by differential scanning calorimetry, X-ray powder diffraction, Fourier transform infrared spectroscopy and in vitro dissolution test.The in vivo pharmacokinetic study was conducted in rats. As a result, OA solid dispersion based on PVP VA 64(OA-PVP) was successfully prepared. In the dissolution medium containing 0.3% SDS, OA-PVP dramatically increased the releasing rate of OA compared with the physical mixture(PM-PVP) and commercial tablet. Furthermore, OA-PVP exhibited higher AUC(P < 0.05) and Cmax(P < 0.05) than PM-PVP and commercial tablet. The superior dissolution property and bioavailability of OA-PVP mainly attributed to the amorphous state of OA in PVP VA64 and the well dispersion caused by thermal melting and shearing. Overall, hot melt extrusion was an efficient strategy to enhance the dissolution rate and oral bioavailability of OA.展开更多
In current study,immediate release solid dispersion(SD)formulation of antiulcer drug lafutidine(LAFT)was developed using hot melt extrusion(HME)technique.Amphiphilic Soluplusused as a primary solubilizing agent,with ...In current study,immediate release solid dispersion(SD)formulation of antiulcer drug lafutidine(LAFT)was developed using hot melt extrusion(HME)technique.Amphiphilic Soluplusused as a primary solubilizing agent,with different concentrations of selected surfactants like PEG 400,Lutrol F127(LF127),Lutrol F68(LF68)were used to investigate their influence on formulations processing via HME.Prepared amorphous glassy solid dispersion was found to be thermodynamically and physicochemically stable.On the contrary,traces of crystalline LAFT not observed in the extrudates according to differential scanning calorimetry(DSC),X-ray diffraction(XRD),scanning electron microscopy(SEM)and Raman spectroscopy.Raman micro spectrometry had the lowest detection limit of LAFT crystals compared with XRD and DSC.Atomic Force microscopy(AFM)studies revealed drugpolymer molecular miscibility and surface interaction at micro level.1HeCOSY NMR spectroscopy confirmed miscibility and interaction between LAFT and Soluplus,with chemical shift drifting and line broadening.MD simulation studies using computational modelling showed intermolecular interaction between molecules.Dissolution rate and solubility of LAFT was enhanced remarkably in developed SD systems.Optimized ratio of polymer and surfactants played crucial role in dissolution rate enhancement of LAFT SD.The obtained results suggested that developed LAFT has promising potential for oral delivery and might be an efficacious approach for enhancing the therapeutic potential of LAFT.展开更多
In this study, bioadhesive mini-matrices of natamycin were prepared for vaginal application by hot-melt extrusion. In addition, melt viscosity measurements, thermogravimetric analysis, in vitro drug release studies an...In this study, bioadhesive mini-matrices of natamycin were prepared for vaginal application by hot-melt extrusion. In addition, melt viscosity measurements, thermogravimetric analysis, in vitro drug release studies and in vitro mucoadhesion test were performed. High molecular weight grades of KlucelTM hydroxypropylcellulose were used as a thermoplastic polymer. TEC and PEG 400 were chosen as plasticizer. According to the obtained results of melt viscosity measurements, the maximum torque of extrudates prepared using PEG 400 increased with increasing drug loading. The thermo-gravimetric analyses showed that natamycin is stable up to 198℃ and this result gives the opportunity to hot melt extrussion process at 90℃. In vitro drug release results showed that the release was extended up to 72 hours and drug release rate increased with increasing drug loading. In respect to the in vitro mucoadhesion test results, the values of work of mucoadhesion were found high as 771,977 mN.mm, 753,199 mN.mm, 686,356 mN.mm for the prepared hot melt extruded mini-matrices. Our results showed that the developed formulations were found worthy of further studies.展开更多
基金financially supported by National Natural Science Foundation of China (No. 81502993)Doctoral Research Funding of Liaoning Province (No. 20141066)+1 种基金General Project in Department of Education of Liaoning Province (No. L2014379)Career Development Program for Young Teachers in Shenyang Pharmaceutical University
文摘The aim of this study was to improve the in vitro dissolution rate and oral bioavailability of oleanolic acid(OA), a water insoluble drug belonging to BCS class IV. Hot melt extrusion(HME) was applied to develop OA amorphous solid dispersions. The characterizations of the optimal formulation were performed by differential scanning calorimetry, X-ray powder diffraction, Fourier transform infrared spectroscopy and in vitro dissolution test.The in vivo pharmacokinetic study was conducted in rats. As a result, OA solid dispersion based on PVP VA 64(OA-PVP) was successfully prepared. In the dissolution medium containing 0.3% SDS, OA-PVP dramatically increased the releasing rate of OA compared with the physical mixture(PM-PVP) and commercial tablet. Furthermore, OA-PVP exhibited higher AUC(P < 0.05) and Cmax(P < 0.05) than PM-PVP and commercial tablet. The superior dissolution property and bioavailability of OA-PVP mainly attributed to the amorphous state of OA in PVP VA64 and the well dispersion caused by thermal melting and shearing. Overall, hot melt extrusion was an efficient strategy to enhance the dissolution rate and oral bioavailability of OA.
基金The author is also thankful to UGC(SAP)for providing the research fellowship and Institute of Chemical Technology,ELITE status(Mumbai,India)for providing all facilities and guidance.The authors are thankful to S.A.I.F.department at Indian Institute of Technology,Mumbai for Raman and 1HeCOSY NMR experimental help and analyses.
文摘In current study,immediate release solid dispersion(SD)formulation of antiulcer drug lafutidine(LAFT)was developed using hot melt extrusion(HME)technique.Amphiphilic Soluplusused as a primary solubilizing agent,with different concentrations of selected surfactants like PEG 400,Lutrol F127(LF127),Lutrol F68(LF68)were used to investigate their influence on formulations processing via HME.Prepared amorphous glassy solid dispersion was found to be thermodynamically and physicochemically stable.On the contrary,traces of crystalline LAFT not observed in the extrudates according to differential scanning calorimetry(DSC),X-ray diffraction(XRD),scanning electron microscopy(SEM)and Raman spectroscopy.Raman micro spectrometry had the lowest detection limit of LAFT crystals compared with XRD and DSC.Atomic Force microscopy(AFM)studies revealed drugpolymer molecular miscibility and surface interaction at micro level.1HeCOSY NMR spectroscopy confirmed miscibility and interaction between LAFT and Soluplus,with chemical shift drifting and line broadening.MD simulation studies using computational modelling showed intermolecular interaction between molecules.Dissolution rate and solubility of LAFT was enhanced remarkably in developed SD systems.Optimized ratio of polymer and surfactants played crucial role in dissolution rate enhancement of LAFT SD.The obtained results suggested that developed LAFT has promising potential for oral delivery and might be an efficacious approach for enhancing the therapeutic potential of LAFT.
基金The authors would like to thank to Scientific and Technological Research Council of Turkey(TUBITAK)(115S476)for their supportThe authors also would like to thank to Pharmaceutical Sciences Research Centre(FABAL)for their support.
文摘In this study, bioadhesive mini-matrices of natamycin were prepared for vaginal application by hot-melt extrusion. In addition, melt viscosity measurements, thermogravimetric analysis, in vitro drug release studies and in vitro mucoadhesion test were performed. High molecular weight grades of KlucelTM hydroxypropylcellulose were used as a thermoplastic polymer. TEC and PEG 400 were chosen as plasticizer. According to the obtained results of melt viscosity measurements, the maximum torque of extrudates prepared using PEG 400 increased with increasing drug loading. The thermo-gravimetric analyses showed that natamycin is stable up to 198℃ and this result gives the opportunity to hot melt extrussion process at 90℃. In vitro drug release results showed that the release was extended up to 72 hours and drug release rate increased with increasing drug loading. In respect to the in vitro mucoadhesion test results, the values of work of mucoadhesion were found high as 771,977 mN.mm, 753,199 mN.mm, 686,356 mN.mm for the prepared hot melt extruded mini-matrices. Our results showed that the developed formulations were found worthy of further studies.
