Previous study has shown that 10-hydroxycamptothecin（HCPT） has well-established pharmacological effects in vitro.However,its in vivo bioavailability is very poor due to various problems,which severely restricts its ...Previous study has shown that 10-hydroxycamptothecin（HCPT） has well-established pharmacological effects in vitro.However,its in vivo bioavailability is very poor due to various problems,which severely restricts its clinical applications.In the present study,phospholipid complex（PC） technology was employed to improve the solubility and bioavailability of HCPT.XRD data confirmed the formation of HCPT-PC.However,our previously prepared HCPT-PC is too sticky,which may result in the slow dissolution rate and negative effects on its absorption.Therefore,we prepared HCPT-PC-solid dispersion（HCPT-PC-SD）and lipid-based formulations of HCPT-PC through simple preparation process.The results showed that the dissolution rate of HCPT-PC was effectively improved by solid dispersion technology,which reached 91.73%in 45 min.Pharmacokinetic study revealed that the AUC_（0-t） of HCPT-PC-SD and HCPT-PC lipid-based formulations was effectively further increased compared with HCPT-PC.Moreover,we found that the combination of SD technology and lipid-base formulations could be a promising drug-delivery system to improve the oral bioavailability of HCPT-PC.In addition,we showed that the bioavailability of HCPT-PC lipid-base formulations was even greater than that of HCPT-PC-SD.In particular,lipid-base formulations could be prepared just by a simple method,suggesting its feasibility of industrialization.展开更多
Quercetin(QUE)has many beneficial biological activities and pharmacological actions in vitro.However,its oral bioavailability in vivo was very poor due to poor solubility,and severely restricted its clinical applicati...Quercetin(QUE)has many beneficial biological activities and pharmacological actions in vitro.However,its oral bioavailability in vivo was very poor due to poor solubility,and severely restricted its clinical applications.In this study,we prepared quercetin solid dispersion(QUE-SD)and quercetin phospholipids complex solid dispersion(QUE-PC-SD)by a solvent evaporation method to improve the absorption of QUE in vivo.The results of XRD of QUE-SD and QUE-PC-SD showed that QUE was dispersed homogeneously in an amorphous or molecular state in QUE-SD and QUE-PC-SD,which could contribute to improve the solubility and dissolution of QUE.The solubility of QUE-SD and QUE-PC-SD was enhanced from(4.03±0.02)μg/mL to(26.91=1=0.06)μg/mL and(30.65±0.06)μg/mL,respectively.The solubility of QUE-PC-SD was higher than that of QUE-SD.In vitro dissolution study,it was showed that the maximum dissolution of QUE(9.57%)from the QUE-SD and QUE-PC-SD was enhanced to 93.81%and 94.16%,respectively.The results of pharmacokinetic experiment indicated that the QUE-SD and QUE-PC-SD exhibited considerable enhancement in the oral bioavailability.The relative bioavailability of QUE-SD and QUE-PC-SD compared with QUE were 149.49%and 198.32%,respectively.In addition,the relative bioavailability of QUE-PC-SD was also higher than that of QUE-SD.Therefore,in regard to drugs with poor solubility and low permeation,an active constituent-PC-SD system could result to a better absorption and higher bioavailability.展开更多
基金Science and Technology Department of Henan province Fund Project(Grant No.144300510019)
文摘Previous study has shown that 10-hydroxycamptothecin（HCPT） has well-established pharmacological effects in vitro.However,its in vivo bioavailability is very poor due to various problems,which severely restricts its clinical applications.In the present study,phospholipid complex（PC） technology was employed to improve the solubility and bioavailability of HCPT.XRD data confirmed the formation of HCPT-PC.However,our previously prepared HCPT-PC is too sticky,which may result in the slow dissolution rate and negative effects on its absorption.Therefore,we prepared HCPT-PC-solid dispersion（HCPT-PC-SD）and lipid-based formulations of HCPT-PC through simple preparation process.The results showed that the dissolution rate of HCPT-PC was effectively improved by solid dispersion technology,which reached 91.73%in 45 min.Pharmacokinetic study revealed that the AUC_（0-t） of HCPT-PC-SD and HCPT-PC lipid-based formulations was effectively further increased compared with HCPT-PC.Moreover,we found that the combination of SD technology and lipid-base formulations could be a promising drug-delivery system to improve the oral bioavailability of HCPT-PC.In addition,we showed that the bioavailability of HCPT-PC lipid-base formulations was even greater than that of HCPT-PC-SD.In particular,lipid-base formulations could be prepared just by a simple method,suggesting its feasibility of industrialization.
基金National Science and Technology Major Projects “Major New Drugs Innovation and Development”(Grant No.2018ZX09201019-002-009)
文摘Quercetin(QUE)has many beneficial biological activities and pharmacological actions in vitro.However,its oral bioavailability in vivo was very poor due to poor solubility,and severely restricted its clinical applications.In this study,we prepared quercetin solid dispersion(QUE-SD)and quercetin phospholipids complex solid dispersion(QUE-PC-SD)by a solvent evaporation method to improve the absorption of QUE in vivo.The results of XRD of QUE-SD and QUE-PC-SD showed that QUE was dispersed homogeneously in an amorphous or molecular state in QUE-SD and QUE-PC-SD,which could contribute to improve the solubility and dissolution of QUE.The solubility of QUE-SD and QUE-PC-SD was enhanced from(4.03±0.02)μg/mL to(26.91=1=0.06)μg/mL and(30.65±0.06)μg/mL,respectively.The solubility of QUE-PC-SD was higher than that of QUE-SD.In vitro dissolution study,it was showed that the maximum dissolution of QUE(9.57%)from the QUE-SD and QUE-PC-SD was enhanced to 93.81%and 94.16%,respectively.The results of pharmacokinetic experiment indicated that the QUE-SD and QUE-PC-SD exhibited considerable enhancement in the oral bioavailability.The relative bioavailability of QUE-SD and QUE-PC-SD compared with QUE were 149.49%and 198.32%,respectively.In addition,the relative bioavailability of QUE-PC-SD was also higher than that of QUE-SD.Therefore,in regard to drugs with poor solubility and low permeation,an active constituent-PC-SD system could result to a better absorption and higher bioavailability.
