Abiraterone acetate(ABTA)was approved by the USFDA in 2011 for treating metastatic castrationresistant prostate cancer(mCRPC).ABTA exhibits poor aqueous solubility,inadequate dissolution,low oral bioavailability(<1...Abiraterone acetate(ABTA)was approved by the USFDA in 2011 for treating metastatic castrationresistant prostate cancer(mCRPC).ABTA exhibits poor aqueous solubility,inadequate dissolution,low oral bioavailability(<10%),and significant positive food effects.To overcome these limitations,in the present work,ABTA solid dispersions(SDs)were developed by using hot melt extrusion technology(HME)with various grades of hydroxypropyl methylcellulose HME(HPMC HME 15LV and 100LV)at different extrusion temperatures.HPMC HME demonstrated the ability to prevent drug precipitation for up to 120 min compared to the free drug(10 min),sustaining the supersaturation state of the drug in the solution phase and demonstrating the spring and parachute effect.The physical interactions of the ABTA SD’s were evaluated by Fourier transform infrared spectroscopy,powder X-ray diffraction,and differential scanning calorimetry confirming the conversion of ABTA into the amorphous state and the molecular interaction between HPMC and ABTA.The bio-relevant dissolution study of ABTA SD showed 2–5 times higher dissolution in fasted(FaSSIF)and fed(FeSSIF)conditions compared to free ABTA.Pharmacokinetic studies in Wistar rats revealed a 6.22 and 4.94-fold increase in Cmax and AUC0–t for the optimized ABTA SD formulation compared to free ABTA.Accelerated stability testing(40±2℃/75±5%RH,90 days)confirmed retained amorphous state,unchanged drug content and dissolution performance for the optimized formulations.The dissolution and bioavailability studies reflected that the prepared SD of ABTA may improve the therapeutic efficacy of ABTA in prostate cancer.The manufacturing technology is scalable and easy to commercialize,revealing the hope of a better treatment strategy for prostate cancer.展开更多
Soil-bentonite(SB)backfills in vertical cutoff walls are used extensively to contain contaminated groundwater.Previous studies show that the hydraulic conductivity of backfill can exceed the typically recommended maxi...Soil-bentonite(SB)backfills in vertical cutoff walls are used extensively to contain contaminated groundwater.Previous studies show that the hydraulic conductivity of backfill can exceed the typically recommended maximum value(k=1×10^(−9) m/s)if exposed to groundwater impacted by organic acids commonly released from uncontrolled landfills and municipal solid waste dumps.Polymer amended backfills exhibit excellent chemical compatibility to metal-laden groundwater.However,few studies to date have explored the effect of organic acid contaminated groundwater on hydraulic performance of polymer amended backfills.This study presents an experimental investigation on the hydraulic performance and microstructural properties of a composite polymer amended backfill used to contain flow of acetic acid-laden groundwater.A series of laboratory experiments were performed to evaluate free-swell indices of the composite polymer amended bentonites,liquid limits of the composite polymer amended and unamended bentonites,and slump heights and hydraulic conductivity(k)values of the amended backfills to acetic acid solutions with varying concentrations.The results were compared with those of the unamended bentonites and unamended backfills reported in a previous study.The results showed that the free-swell index and liquid limit of the amended bentonites were higher than those of the unamended bentonites.Permeation with acetic acid solutions with concentrations ranging from 40 mmol/L to 320 mmol/L conducted on the amended backfill only resulted in an increase in k of less than a factor of about 10 related to that based on permeation with tap water(4.41×10^(−11)-1.68×10^(−10) m/s to acetic acid solution versus 1.65×10^(−11) m/s to tap water).Mechanisms contributing to enhanced chemical compatibility of amended backfill were ascertained based on scanning electron microscopy,mercury intrusion porosimetry,and zeta potential analyses.展开更多
文摘Abiraterone acetate(ABTA)was approved by the USFDA in 2011 for treating metastatic castrationresistant prostate cancer(mCRPC).ABTA exhibits poor aqueous solubility,inadequate dissolution,low oral bioavailability(<10%),and significant positive food effects.To overcome these limitations,in the present work,ABTA solid dispersions(SDs)were developed by using hot melt extrusion technology(HME)with various grades of hydroxypropyl methylcellulose HME(HPMC HME 15LV and 100LV)at different extrusion temperatures.HPMC HME demonstrated the ability to prevent drug precipitation for up to 120 min compared to the free drug(10 min),sustaining the supersaturation state of the drug in the solution phase and demonstrating the spring and parachute effect.The physical interactions of the ABTA SD’s were evaluated by Fourier transform infrared spectroscopy,powder X-ray diffraction,and differential scanning calorimetry confirming the conversion of ABTA into the amorphous state and the molecular interaction between HPMC and ABTA.The bio-relevant dissolution study of ABTA SD showed 2–5 times higher dissolution in fasted(FaSSIF)and fed(FeSSIF)conditions compared to free ABTA.Pharmacokinetic studies in Wistar rats revealed a 6.22 and 4.94-fold increase in Cmax and AUC0–t for the optimized ABTA SD formulation compared to free ABTA.Accelerated stability testing(40±2℃/75±5%RH,90 days)confirmed retained amorphous state,unchanged drug content and dissolution performance for the optimized formulations.The dissolution and bioavailability studies reflected that the prepared SD of ABTA may improve the therapeutic efficacy of ABTA in prostate cancer.The manufacturing technology is scalable and easy to commercialize,revealing the hope of a better treatment strategy for prostate cancer.
基金National Natural Science Foundation of China (Grant No.42177133)Primary R&D Plan of Jiangsu Province (Grant No.BE2022830)Primary R&D Plan of Anhui Province (Grant No.2023t07020018).
文摘Soil-bentonite(SB)backfills in vertical cutoff walls are used extensively to contain contaminated groundwater.Previous studies show that the hydraulic conductivity of backfill can exceed the typically recommended maximum value(k=1×10^(−9) m/s)if exposed to groundwater impacted by organic acids commonly released from uncontrolled landfills and municipal solid waste dumps.Polymer amended backfills exhibit excellent chemical compatibility to metal-laden groundwater.However,few studies to date have explored the effect of organic acid contaminated groundwater on hydraulic performance of polymer amended backfills.This study presents an experimental investigation on the hydraulic performance and microstructural properties of a composite polymer amended backfill used to contain flow of acetic acid-laden groundwater.A series of laboratory experiments were performed to evaluate free-swell indices of the composite polymer amended bentonites,liquid limits of the composite polymer amended and unamended bentonites,and slump heights and hydraulic conductivity(k)values of the amended backfills to acetic acid solutions with varying concentrations.The results were compared with those of the unamended bentonites and unamended backfills reported in a previous study.The results showed that the free-swell index and liquid limit of the amended bentonites were higher than those of the unamended bentonites.Permeation with acetic acid solutions with concentrations ranging from 40 mmol/L to 320 mmol/L conducted on the amended backfill only resulted in an increase in k of less than a factor of about 10 related to that based on permeation with tap water(4.41×10^(−11)-1.68×10^(−10) m/s to acetic acid solution versus 1.65×10^(−11) m/s to tap water).Mechanisms contributing to enhanced chemical compatibility of amended backfill were ascertained based on scanning electron microscopy,mercury intrusion porosimetry,and zeta potential analyses.
