Lappaconitine is a water-insoluble drug, which was used as model drug in this study. Currently, two osmotically controlled delivery systems that are widely used for water-insoluble drug are monolithic osmotic tablet ...Lappaconitine is a water-insoluble drug, which was used as model drug in this study. Currently, two osmotically controlled delivery systems that are widely used for water-insoluble drug are monolithic osmotic tablet （MOT） and push-pull osmotic pump （PPOP）. In the present study, lappaconitine solid dispersion monolithic osmotic tablet （lappaconitine-SD-MOT） and lappaconitine-PPOP were developed. The prepared lappaconitine-PPOP was able to delivery drug at the rate of approximate zero-order （r = 0.9931）, and the cumulative release was above 95.0%. The lappaconitine-SD-MOT showed a comparatively poor linearity when the data were plotted according to the zero-order equation （r = 0.9798）, and the cumulative release was 84.69%. Lappaconitine-PPOP exhibited better controlled drug release （higher regression value） compared with lappaconitine-SD-MOT. The similarity index （f2） between lappaconitine-PPOP and lappaconitine-SD-MOT was 49.1 （〈50）. A clear difference of drug release characteristics between the lappaconitine-SD-MOT and lappaconitine-PPOP was revealed. It indicated that the drug release performance of lappaconitine-PPOP could gain favorable zero-order kinetics and higher cumulative release compared with lappaconitine-SD-MOT. Therefore, these results suggested that PPOP was still a very effective device for the delivery of poorly water-soluble drug with zero-order pattern.展开更多
Defining and visualizing the three-dimensional(3 D) structures of pharmaceuticals provides a new and important tool to elucidate the phenomenal behavior and underlying mechanisms of drug delivery systems. The mechanis...Defining and visualizing the three-dimensional(3 D) structures of pharmaceuticals provides a new and important tool to elucidate the phenomenal behavior and underlying mechanisms of drug delivery systems. The mechanism of drug release from complex structured dosage forms, such as bilayer osmotic pump tablets, has not been investigated widely for most solid 3 D structures. In this study, bilayer osmotic pump tablets undergoing dissolution, as well as after dissolution in a desiccated solid state were examined, and visualized by synchrotron radiation micro-computed tomography(SR-μCT). In situ formed 3 D structures at different in vitro drug release states were characterized comprehensively. A distinct movement pattern of NaCl crystals from the push layer to the drug layer was observed, beneath the semi-permeable coating in the desiccated tablet samples. The 3 D structures at different dissolution time revealed that the pushing upsurge in the bilayer osmotic pump tablet was directed via peripheral“roadways”. Typically, different regions of the osmotic front, infiltration region, and dormant region were classified in the push layer during the dissolution of drug from tablet samples. According to the observed3 D microstructures, a “subterranean river model” for the drug release mechanism has been defined to explain the drug release mechanism.展开更多
基金Science and Technology Department of Henan Pro vince Fund Project(Grant No.144300510019)
文摘Lappaconitine is a water-insoluble drug, which was used as model drug in this study. Currently, two osmotically controlled delivery systems that are widely used for water-insoluble drug are monolithic osmotic tablet （MOT） and push-pull osmotic pump （PPOP）. In the present study, lappaconitine solid dispersion monolithic osmotic tablet （lappaconitine-SD-MOT） and lappaconitine-PPOP were developed. The prepared lappaconitine-PPOP was able to delivery drug at the rate of approximate zero-order （r = 0.9931）, and the cumulative release was above 95.0%. The lappaconitine-SD-MOT showed a comparatively poor linearity when the data were plotted according to the zero-order equation （r = 0.9798）, and the cumulative release was 84.69%. Lappaconitine-PPOP exhibited better controlled drug release （higher regression value） compared with lappaconitine-SD-MOT. The similarity index （f2） between lappaconitine-PPOP and lappaconitine-SD-MOT was 49.1 （〈50）. A clear difference of drug release characteristics between the lappaconitine-SD-MOT and lappaconitine-PPOP was revealed. It indicated that the drug release performance of lappaconitine-PPOP could gain favorable zero-order kinetics and higher cumulative release compared with lappaconitine-SD-MOT. Therefore, these results suggested that PPOP was still a very effective device for the delivery of poorly water-soluble drug with zero-order pattern.
基金the National Nature Science Foundation of China (Nos.81803446,81803441 and 81773645)Key Program for International Science and Technology Cooperation Projects of China (2020YFE0201700)the Youth Innovation Promotion Association of CAS (2018323)。
文摘Defining and visualizing the three-dimensional(3 D) structures of pharmaceuticals provides a new and important tool to elucidate the phenomenal behavior and underlying mechanisms of drug delivery systems. The mechanism of drug release from complex structured dosage forms, such as bilayer osmotic pump tablets, has not been investigated widely for most solid 3 D structures. In this study, bilayer osmotic pump tablets undergoing dissolution, as well as after dissolution in a desiccated solid state were examined, and visualized by synchrotron radiation micro-computed tomography(SR-μCT). In situ formed 3 D structures at different in vitro drug release states were characterized comprehensively. A distinct movement pattern of NaCl crystals from the push layer to the drug layer was observed, beneath the semi-permeable coating in the desiccated tablet samples. The 3 D structures at different dissolution time revealed that the pushing upsurge in the bilayer osmotic pump tablet was directed via peripheral“roadways”. Typically, different regions of the osmotic front, infiltration region, and dormant region were classified in the push layer during the dissolution of drug from tablet samples. According to the observed3 D microstructures, a “subterranean river model” for the drug release mechanism has been defined to explain the drug release mechanism.
