The sample preparation of samples conlaining bovine serum albumin（BSA）,e.g..as used in transdermal Franz diffusion cell（FDC） solutions,was evaluated using an analytical qualily-by-design（QbD）approach.Traditional...The sample preparation of samples conlaining bovine serum albumin（BSA）,e.g..as used in transdermal Franz diffusion cell（FDC） solutions,was evaluated using an analytical qualily-by-design（QbD）approach.Traditional precipitation of BSA by adding an equal volume of organic solvent,often successfully used with conventional HPLC-PDA,was found insufficiently robust when novel fused-core HPLC and/or UPLC-MS methods were used.In this study,three factors（acetonitrile（%）.formic acid（%） and boiling time（min）） were included in the experimental design to determine an optimal and more suitable sample treatment of BSAcontaining FDC solutions.Using a QbD and Derringer desirability（D） approach,combining BSA loss,dilution factor and variability,we constructed an optimal working space with the edge of failure defined as D〈0.9.The design space is modelled and is confirmed to have an ACN range of 83 ± 3% and FA content of 1 ±0.25%.展开更多
Febuxostat(FXT)is useful in treating hyperuricemia and chronic gout.However,it has limited bioavailability orally due to its low solubility and short half-life.This results in the need for more frequent and larger dos...Febuxostat(FXT)is useful in treating hyperuricemia and chronic gout.However,it has limited bioavailability orally due to its low solubility and short half-life.This results in the need for more frequent and larger doses,increasing the likelihood of adverse effects.Against this background,the current study was established to prepare and optimize an FXT-loaded proniosomal gel using the coacervation-phase separation method.A Quality-by-Design(QbD)methodology was used to ensure the quality of the finished product by assessing how critical process parameters and critical material attributes(CMAs)affected the proniosomal gel’s critical quality attributes.Box-Behnken design was employed to explore the effect of CMAs such as the amount of cholesterol,Span 40,and Span 60 on particle size and entrapment efficiency.The optimized proniosomes had a particle size and percentage entrapment efficiency of 193.7±2.26 nm and 85.3%±0.89%,respectively.Scanning electron microscopy was used to examine the surface morphology of the optimized formulation.The developed formulation was also subjected to in vitro drug release and ex vivo permeation studies,which established the efficiency of the prepared proniosomal gel.Stability studies also established the fact that the prepared formulation is stable to variations in temperature for up to 6 months.展开更多
In comparison to the established twin-screw machines,the application of a planetary roller granulator for continuous operation of melt granulation is a promising alternative based on the unique process concept.An init...In comparison to the established twin-screw machines,the application of a planetary roller granulator for continuous operation of melt granulation is a promising alternative based on the unique process concept.An initial study focused on the material transport during processing as a key driver for the overall performance.Hereby,the impact of direct process parameters on the residence time distribution was the main objective.These investigations are complemented in this study by considering the free processing volume,which is defined by the number of planetary spindles applied within a module.The impact on the processing conditions is evaluated with respect to the process setting in terms of feed rate and rotation speed.The results highlight the potential of altering the underlying transport function in planetary roller melt granulation(PRMG)via the investigated direct process and equipment parameters.The impact of the feed rate is lower in comparison,while a higher rotation speed as well as a higher free processing volume promote material mixing.Moreover,a normalization of the determined residence time distribution(RTD)model data was feasible with respect to the process settings and the number of applied planetary spindles in the processing zone.This demonstrates the key role of the free processing volume in the fundamental mechanisms of material transport and mixing during PRMG.展开更多
基金the Special Research Fund of Ghent University(BOF 01D23812 to Lien Taevernier and BOF O1J22510 to Evelien Wynendaele and Professor Bart De Spiegeleer)the Institute for the Promotion of Innovation through Science and Technology in Flanders(IWT 101529 to Matthias D'Hondt)for their financial funding
文摘The sample preparation of samples conlaining bovine serum albumin（BSA）,e.g..as used in transdermal Franz diffusion cell（FDC） solutions,was evaluated using an analytical qualily-by-design（QbD）approach.Traditional precipitation of BSA by adding an equal volume of organic solvent,often successfully used with conventional HPLC-PDA,was found insufficiently robust when novel fused-core HPLC and/or UPLC-MS methods were used.In this study,three factors（acetonitrile（%）.formic acid（%） and boiling time（min）） were included in the experimental design to determine an optimal and more suitable sample treatment of BSAcontaining FDC solutions.Using a QbD and Derringer desirability（D） approach,combining BSA loss,dilution factor and variability,we constructed an optimal working space with the edge of failure defined as D〈0.9.The design space is modelled and is confirmed to have an ACN range of 83 ± 3% and FA content of 1 ±0.25%.
文摘Febuxostat(FXT)is useful in treating hyperuricemia and chronic gout.However,it has limited bioavailability orally due to its low solubility and short half-life.This results in the need for more frequent and larger doses,increasing the likelihood of adverse effects.Against this background,the current study was established to prepare and optimize an FXT-loaded proniosomal gel using the coacervation-phase separation method.A Quality-by-Design(QbD)methodology was used to ensure the quality of the finished product by assessing how critical process parameters and critical material attributes(CMAs)affected the proniosomal gel’s critical quality attributes.Box-Behnken design was employed to explore the effect of CMAs such as the amount of cholesterol,Span 40,and Span 60 on particle size and entrapment efficiency.The optimized proniosomes had a particle size and percentage entrapment efficiency of 193.7±2.26 nm and 85.3%±0.89%,respectively.Scanning electron microscopy was used to examine the surface morphology of the optimized formulation.The developed formulation was also subjected to in vitro drug release and ex vivo permeation studies,which established the efficiency of the prepared proniosomal gel.Stability studies also established the fact that the prepared formulation is stable to variations in temperature for up to 6 months.
文摘In comparison to the established twin-screw machines,the application of a planetary roller granulator for continuous operation of melt granulation is a promising alternative based on the unique process concept.An initial study focused on the material transport during processing as a key driver for the overall performance.Hereby,the impact of direct process parameters on the residence time distribution was the main objective.These investigations are complemented in this study by considering the free processing volume,which is defined by the number of planetary spindles applied within a module.The impact on the processing conditions is evaluated with respect to the process setting in terms of feed rate and rotation speed.The results highlight the potential of altering the underlying transport function in planetary roller melt granulation(PRMG)via the investigated direct process and equipment parameters.The impact of the feed rate is lower in comparison,while a higher rotation speed as well as a higher free processing volume promote material mixing.Moreover,a normalization of the determined residence time distribution(RTD)model data was feasible with respect to the process settings and the number of applied planetary spindles in the processing zone.This demonstrates the key role of the free processing volume in the fundamental mechanisms of material transport and mixing during PRMG.
