The clinical pharmacokinetics of osmotic pump controlled release tablets of terazosin hydrochloride in healthy volunteers was studied.A sensitive and rapid HPLC method was used to determine the terazosin plasma concen...The clinical pharmacokinetics of osmotic pump controlled release tablets of terazosin hydrochloride in healthy volunteers was studied.A sensitive and rapid HPLC method was used to determine the terazosin plasma concentrations,and single and multiple doses of terazosin hydrochloride regular tablets（reference tablets）and osmotic pump controlled release tablets were orally administrated in randomized crossover design.The results showed that the C_（max）of the reference tablets after single oral dose（（120.56±23.15）ng/mL）in 20 healthy volunteers was significantly higher than that of controlled release tablets （（95.27±16.35）ng/mL）.The T_（max）of the controlled release tablets（（2.65±0.82）h）was significantly longer than that of reference tablets（（1.27±0.61）h）（P0.05）.The relative bioavailability of the controlled release tablets was found to be（105.85±6.12）%. The multiple oral dose pharmacokinetic parameters of the regular tablets and controlled release tablets were as follows：AUC_（SS） were（1275.17±175.35）and（1382.65±205.31）ng·h/mL respectively,C_（max）were（128.15±22.37）and（98.57±18.16）ng/mL respectively,T_（max）were（1.35±0.71）and（2.76±0.85）h respectively,C_（av）were（53.13±9.12）and（57.61±9.25）ng/mL respectively, and DF were（2.25±0.26）%and（1.62±0.25）%respectively.The relative bioavailability of the controlled release tablets to the reference tablets was（108.43±6.26）%.The controlled release tablet of terazosin hydrochloride was bioequivalent to the reference tablet.The controlled release tablet exhibited a sustained-release property with a significantly longer T_（max）and lower C_（max）.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
Aim To study unitary-core osmotic pump tablet for delivering water-insoluble drug for 24 hours. Methods Unitary-core osmotic pump tablet was prepared using nifedipine as the model drug. The effects of various core for...Aim To study unitary-core osmotic pump tablet for delivering water-insoluble drug for 24 hours. Methods Unitary-core osmotic pump tablet was prepared using nifedipine as the model drug. The effects of various core formulation variables on drug release were studied. Results Polyethylene oxide and potassium chloride have comparable positive effects on drug release, whereas, nifedipine has markedly negative effect on drug release. Conclusion Unitary-core osmotic pump tablet is very easy in preparation and it can deliver water-insoluble drug in substantially constant rate for 24 hours.展开更多
文摘The clinical pharmacokinetics of osmotic pump controlled release tablets of terazosin hydrochloride in healthy volunteers was studied.A sensitive and rapid HPLC method was used to determine the terazosin plasma concentrations,and single and multiple doses of terazosin hydrochloride regular tablets（reference tablets）and osmotic pump controlled release tablets were orally administrated in randomized crossover design.The results showed that the C_（max）of the reference tablets after single oral dose（（120.56±23.15）ng/mL）in 20 healthy volunteers was significantly higher than that of controlled release tablets （（95.27±16.35）ng/mL）.The T_（max）of the controlled release tablets（（2.65±0.82）h）was significantly longer than that of reference tablets（（1.27±0.61）h）（P0.05）.The relative bioavailability of the controlled release tablets was found to be（105.85±6.12）%. The multiple oral dose pharmacokinetic parameters of the regular tablets and controlled release tablets were as follows：AUC_（SS） were（1275.17±175.35）and（1382.65±205.31）ng·h/mL respectively,C_（max）were（128.15±22.37）and（98.57±18.16）ng/mL respectively,T_（max）were（1.35±0.71）and（2.76±0.85）h respectively,C_（av）were（53.13±9.12）and（57.61±9.25）ng/mL respectively, and DF were（2.25±0.26）%and（1.62±0.25）%respectively.The relative bioavailability of the controlled release tablets to the reference tablets was（108.43±6.26）%.The controlled release tablet of terazosin hydrochloride was bioequivalent to the reference tablet.The controlled release tablet exhibited a sustained-release property with a significantly longer T_（max）and lower C_（max）.
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.
文摘Aim To study unitary-core osmotic pump tablet for delivering water-insoluble drug for 24 hours. Methods Unitary-core osmotic pump tablet was prepared using nifedipine as the model drug. The effects of various core formulation variables on drug release were studied. Results Polyethylene oxide and potassium chloride have comparable positive effects on drug release, whereas, nifedipine has markedly negative effect on drug release. Conclusion Unitary-core osmotic pump tablet is very easy in preparation and it can deliver water-insoluble drug in substantially constant rate for 24 hours.
