An explicit illustration of pulmonary delivery processes(PDPs)was a prerequisite for the formulation design and optimization of carrier-based DPIs.However,the current evaluation approaches for DPIs could not provide p...An explicit illustration of pulmonary delivery processes(PDPs)was a prerequisite for the formulation design and optimization of carrier-based DPIs.However,the current evaluation approaches for DPIs could not provide precise investigation of each PDP separately,or the approaches merely used a simplified and idealized model.In the present study,a novel modular modified Sympatec HELOS Real-time monitoring;Modular modification;Carrier;Air flow rate;Mechanism of drug delivery(MMSH)was developed to fully investigate the mechanism of each PDP separately in real-time.An inhaler device,artificial throat and pre-separator were separately integrated with a Sympatec HELOS.The dispersion and fluidization,transportation,detachment and deposition processes of pulmonary delivery for model DPIs were explored under different flow rates.Moreover,time-sliced measurements were used to monitor the PDPs in real-time.The Next Generation Impactor(NGI)was applied to determine the aerosolization performance of the model DPIs.The release profiles of the drug particles,drug aggregations and carriers were obtained by MMSH in real-time.Each PDP of the DPIs was analyzed in detail.Moreover,a positive correlation was established between the total release amount of drug particles and the fine particle fraction(FPF)values(R^2=0.9898).The innovative MMSH was successfully developed and was capable of illustrating the PDPs and the mechanism of carrier-based DPIs,providing a theoretical basis for the design and optimization of carrier-based DPIs.展开更多
Topological design of service networks is studied in the paper. Quantitative model and algorithm minimizing cost of processing and delivery is described. Algorithm solving combinatorial problem of optimal design based...Topological design of service networks is studied in the paper. Quantitative model and algorithm minimizing cost of processing and delivery is described. Algorithm solving combinatorial problem of optimal design based on binary partitioning, a parametric search and dynamic programming optimization of a binary tree is described and demonstrated in numeric example.展开更多
Dry powder inhalers(DPIs) had been widely used in lung diseases on account of direct pulmonary delivery, good drug stability and satisfactory patient compliance. However, an indistinct understanding of pulmonary deliv...Dry powder inhalers(DPIs) had been widely used in lung diseases on account of direct pulmonary delivery, good drug stability and satisfactory patient compliance. However, an indistinct understanding of pulmonary delivery processes(PDPs) hindered the development of DPIs. Most current evaluation methods explored the PDPs with over-simplified models, leading to uncompleted investigations of the whole or partial PDPs. In the present research, an innovative modular process analysis platform(MPAP) was applied to investigate the detailed mechanisms of each PDP of DPIs with different carrier particle sizes(CPS). The MPAP was composed of a laser particle size analyzer, an inhaler device,an artificial throat and a pre-separator, to investigate the fluidization and dispersion, transportation,detachment and deposition process of DPIs. The release profiles of drug, drug aggregation and carrier were monitored in real-time. The influence of CPS on PDPs and corresponding mechanisms were explored. The powder properties of the carriers were investigated by the optical profiler and Freeman Technology four powder rheometer. The next generation impactor was employed to explore the aerosolization performance of DPIs. The novel MPAP was successfully applied in exploring the comprehensive mechanism of PDPs, which had enormous potential to be used to investigate and develop DPIs.展开更多
Shale gas reservoirs are found all over the world.Their endowment worldwide is estimated at 10,000 tcf by the GFREE team in the Schulich School of Engineering at the University of Calgary.The shale gas work and produc...Shale gas reservoirs are found all over the world.Their endowment worldwide is estimated at 10,000 tcf by the GFREE team in the Schulich School of Engineering at the University of Calgary.The shale gas work and production initiated successfully in the Unites States and extended to Canada will have application,with modifications,in several other countries in the future.The‘modifications’qualifier is important as each shale gas reservoir should be considered as a research project by itself to avoid fiascos and major financial losses.Shale gas reservoirs are best represented by at least quadruple porosity models.Some of the production obtained from shale reservoirs is dominated by diffusion flow.The approximate boundary between viscous and diffusion-like flow is estimated with Knudsen number.Viscous flow is present,for example,when the architecture of the rock is dominated by mega pore throat,macro pore throat,meso pore throat and sometimes micro pore throat.Diffusion flow on the other hand is observed at the nano pore throat level.The process speed concept has been used successfully in conventional reservoirs for several decades.However,the concept discussed in this paper for tight gas and shale gas reservoirs,with the support of core data,has been developed only recently,and permits differentiating between viscous and diffusion dominated flow.This is valuable,for example,in those cases where the formation to be developed is composed of alternating stacked layers of tight sands and shales,or where there are lateral variations due to facies changes.An approach to develop the concept of a super-giant shale gas reservoir is presented as well as a description of GFREE,a successful research program for tight formations.The paper closes with examples of detailed original gas-in-place(OGIP)calculations for 3 North American shale gas reservoirs including free gas in natural fractures and the porous network within the organic matter,gas in the non-organic matter,adsorbed gas,and estimates of free gas within fractures created during hydraulic fracturing jobs.The examples show that the amount of free gas in shale reservoirs,as a percent of the total OGIP,is probably larger than considered previously in the literature.展开更多
基金funded by the National Natural Science Foundation of China(81673375 and 81703431)the Science and Technology Foundation Guangzhou(201509030006,China)the National Students Innovation Training Program of China(201901390)
文摘An explicit illustration of pulmonary delivery processes(PDPs)was a prerequisite for the formulation design and optimization of carrier-based DPIs.However,the current evaluation approaches for DPIs could not provide precise investigation of each PDP separately,or the approaches merely used a simplified and idealized model.In the present study,a novel modular modified Sympatec HELOS Real-time monitoring;Modular modification;Carrier;Air flow rate;Mechanism of drug delivery(MMSH)was developed to fully investigate the mechanism of each PDP separately in real-time.An inhaler device,artificial throat and pre-separator were separately integrated with a Sympatec HELOS.The dispersion and fluidization,transportation,detachment and deposition processes of pulmonary delivery for model DPIs were explored under different flow rates.Moreover,time-sliced measurements were used to monitor the PDPs in real-time.The Next Generation Impactor(NGI)was applied to determine the aerosolization performance of the model DPIs.The release profiles of the drug particles,drug aggregations and carriers were obtained by MMSH in real-time.Each PDP of the DPIs was analyzed in detail.Moreover,a positive correlation was established between the total release amount of drug particles and the fine particle fraction(FPF)values(R^2=0.9898).The innovative MMSH was successfully developed and was capable of illustrating the PDPs and the mechanism of carrier-based DPIs,providing a theoretical basis for the design and optimization of carrier-based DPIs.
文摘Topological design of service networks is studied in the paper. Quantitative model and algorithm minimizing cost of processing and delivery is described. Algorithm solving combinatorial problem of optimal design based on binary partitioning, a parametric search and dynamic programming optimization of a binary tree is described and demonstrated in numeric example.
基金funded by the Fundamental Research Funds for the Central Universities(Nos.21620434 and 2162014,China)the National Natural Science Foundation of China(Nos.81673375 and 81703431)+1 种基金the Science and Technology Foundation Guangzhou(No.201509030006,China)the National Students Innovation Training Program of China(No.201901390,China)。
文摘Dry powder inhalers(DPIs) had been widely used in lung diseases on account of direct pulmonary delivery, good drug stability and satisfactory patient compliance. However, an indistinct understanding of pulmonary delivery processes(PDPs) hindered the development of DPIs. Most current evaluation methods explored the PDPs with over-simplified models, leading to uncompleted investigations of the whole or partial PDPs. In the present research, an innovative modular process analysis platform(MPAP) was applied to investigate the detailed mechanisms of each PDP of DPIs with different carrier particle sizes(CPS). The MPAP was composed of a laser particle size analyzer, an inhaler device,an artificial throat and a pre-separator, to investigate the fluidization and dispersion, transportation,detachment and deposition process of DPIs. The release profiles of drug, drug aggregation and carrier were monitored in real-time. The influence of CPS on PDPs and corresponding mechanisms were explored. The powder properties of the carriers were investigated by the optical profiler and Freeman Technology four powder rheometer. The next generation impactor was employed to explore the aerosolization performance of DPIs. The novel MPAP was successfully applied in exploring the comprehensive mechanism of PDPs, which had enormous potential to be used to investigate and develop DPIs.
基金Parts of this work were funded by the Natural Sciences and Engineering Research Council of Canada(NSERC agreement 347825-06)ConocoPhillips(agreement 4204638)+2 种基金Alberta Innovates Energy and Environment Solutions(AERI agreement 1711)the Schulich School of Engineering at the University of Calgary and Servipetrol Ltd.Porosities and permeabilities from Nikanassin drill cuttings were determined by Nisael Solano of the University of Calgary using Darcylog equipment provided by Mr.Roland Lenormand of Cydarex in Paris,FranceThe 3D hydraulic fracturing simulation was performed using GOHFER,contributed to the GFREE Research program by R.D.Barree of B&A and Kevin Svatek of Core Lab.
文摘Shale gas reservoirs are found all over the world.Their endowment worldwide is estimated at 10,000 tcf by the GFREE team in the Schulich School of Engineering at the University of Calgary.The shale gas work and production initiated successfully in the Unites States and extended to Canada will have application,with modifications,in several other countries in the future.The‘modifications’qualifier is important as each shale gas reservoir should be considered as a research project by itself to avoid fiascos and major financial losses.Shale gas reservoirs are best represented by at least quadruple porosity models.Some of the production obtained from shale reservoirs is dominated by diffusion flow.The approximate boundary between viscous and diffusion-like flow is estimated with Knudsen number.Viscous flow is present,for example,when the architecture of the rock is dominated by mega pore throat,macro pore throat,meso pore throat and sometimes micro pore throat.Diffusion flow on the other hand is observed at the nano pore throat level.The process speed concept has been used successfully in conventional reservoirs for several decades.However,the concept discussed in this paper for tight gas and shale gas reservoirs,with the support of core data,has been developed only recently,and permits differentiating between viscous and diffusion dominated flow.This is valuable,for example,in those cases where the formation to be developed is composed of alternating stacked layers of tight sands and shales,or where there are lateral variations due to facies changes.An approach to develop the concept of a super-giant shale gas reservoir is presented as well as a description of GFREE,a successful research program for tight formations.The paper closes with examples of detailed original gas-in-place(OGIP)calculations for 3 North American shale gas reservoirs including free gas in natural fractures and the porous network within the organic matter,gas in the non-organic matter,adsorbed gas,and estimates of free gas within fractures created during hydraulic fracturing jobs.The examples show that the amount of free gas in shale reservoirs,as a percent of the total OGIP,is probably larger than considered previously in the literature.
