Architectural design technology management covers multiple aspects,including the formulation of technical standards,method selection,etc.It plays a key role in design quality,such as establishing a closed-loop managem...Architectural design technology management covers multiple aspects,including the formulation of technical standards,method selection,etc.It plays a key role in design quality,such as establishing a closed-loop management mechanism for the entire process and utilizing BIM collaborative platforms.It also introduces the application of techniques such as parametric design and the construction of quality prediction models.Simultaneously elaborating on the formulation of enterprise standards and other related content,this paper finally proposes an integrated solution while pointing out development bottlenecks and prospects.展开更多
Northwest Electric Power Design Institute (NWEPDI)was established in 1956. The institute undertakes the engineering exploration, survey and design of thermal electric power plant, conventional island of nuclear power ...Northwest Electric Power Design Institute (NWEPDI)was established in 1956. The institute undertakes the engineering exploration, survey and design of thermal electric power plant, conventional island of nuclear power plant, power transmission and substation projects, design of the 1st and 2nd class pressure vessels, electric power system planning, environmental protection engineering monitoring, assessment and design, various industrial and civil architectural design and the scicntific research and technical development tasks of corresponding specialities. The institute展开更多
Knee osteoarthritis(KOA),characterized by heterogeneous arthritic manifestations and complex peripheral joint disorder,is one of the leading causes of disability worldwide,which has become a high burden due to the mul...Knee osteoarthritis(KOA),characterized by heterogeneous arthritic manifestations and complex peripheral joint disorder,is one of the leading causes of disability worldwide,which has become a high burden due to the multifactorial nature and the deficiency of available disease-modifying treatments.The application of mesenchymal stem/stromal cells(MSCs)as therapeutic drugs has provided novel treatment options for diverse degenerative and chronic diseases including KOA.However,the complexity and specificity of the“live”cells have posed challenges for MSC-based drug development and the concomitant scale-up preparation from laboratory to industrialization.For instance,despite the considerable progress in ex vivo cell culture technology for fulfilling the robust development of drug conversion and clinical trials,yet significant challenges remain in obtaining regulatory approvals.Thus,there’s an urgent need for the research and development of MSC drugs for KOA.In this review,we provide alternative solution strategies for the preparation of MSC drugs on the basis of the principle of quality by design,including designing the cell production processes,quality control,and clinical applications.In detail,we mainly focus on the quality by design method for MSC manufacturing in standard cell-culturing factories for the treatment of KOA by using the Quality Target Product Profile as a starting point to determine potential critical quality attributes and to establish relationships between critical material attributes and critical process parameters.Collectively,this review aims to meet product performance and robust process design,and should help to reduce the gap between compliant products and the production of compliant good manufacturing practice.展开更多
The assessment of in situ permeability of rock mass is challenging for large-scale projects such as reservoirs created by dams,where water tightness issues are of prime importance.The in situ permeability is strongly ...The assessment of in situ permeability of rock mass is challenging for large-scale projects such as reservoirs created by dams,where water tightness issues are of prime importance.The in situ permeability is strongly related to the frequency and distribution of discontinuities in the rock mass and quantified by rock quality designation(RQD).This paper analyzes the data of hydraulic conductivity and discontinuities sampled at different depths during the borehole investigations in the limestone and sandstone formations for the construction of hydraulic structures in Oman.Cores recovered from boreholes provide RQD data,and in situ Lugeon tests elucidate the permeability.A modern technique of multivariate adaptive regression splines(MARS)assisted in correlating permeability and RQD along with the depth.In situ permeability shows a declining trend with increasing RQD,and the depth of investigation is within 50 m.This type of relationship can be developed based on detailed initial investigations at the site where the hydraulic conductivity of discontinuous rocks is required to be delineated.The relationship can approximate the permeability by only measuring the RQD in later investigations on the same site,thus saving the time and cost of the site investigations.The applicability of the relationship developed in this study to another location requires a lithological similarity of the rock mass that can be verified through preliminary investigation at the site.展开更多
Rock quality designation(RQD)has been considered as a one-dimensional jointing degree property since it should be determined by measuring the core lengths obtained from drilling.Anisotropy index of jointing degree(AI_...Rock quality designation(RQD)has been considered as a one-dimensional jointing degree property since it should be determined by measuring the core lengths obtained from drilling.Anisotropy index of jointing degree(AI_(jd))was formulated by Zheng et al.(2018)by considering maximum and minimum values of RQD for a jointed rock medium in three-dimensional space.In accordance with spacing terminology by ISRM(1981),defining the jointing degree for the rock masses composed of extremely closely spaced joints as well as for the rock masses including widely to extremely widely spaced joints is practically impossible because of the use of 10 cm as a threshold value in the conventional form of RQD.To overcome this limitation,theoretical RQD(TRQD_(t))introduced by Priest and Hudson(1976)can be taken into consideration only when the statistical distribution of discontinuity spacing has a negative exponential distribution.Anisotropy index of the jointing degree was improved using TRQD_(t) which was adjusted to wider joint spacing by considering Priest(1993)’s recommendation on the use of variable threshold value(t)in TRQD_(t) formulation.After applications of the improved anisotropy index of a jointing degree(AI'_(jd))to hypothetical jointed rock mass cases,the effect of persistency of joints on structural anisotropy of rock mass was introduced to the improved AI'_(jd) formulation by considering the ratings of persistency of joints as proposed by Bieniawski(1989)’s rock mass rating(RMR)classification.Two real cases were assessed in the stratified marl and the columnar basalt using the weighted anisotropy index of jointing degree(W_AI'_(jd)).A structural anisotropy classification was developed using the RQD classification proposed by Deere(1963).The proposed methodology is capable of defining the structural anisotropy of a rock mass including joint pattern from extremely closely to extremely widely spaced joints.展开更多
From a regulatory perspective,drug quality consistency evaluation must concern different processes used for the same drug.In this study,an assessment strategy based on quality by design(QbD)was developed for populatio...From a regulatory perspective,drug quality consistency evaluation must concern different processes used for the same drug.In this study,an assessment strategy based on quality by design(QbD)was developed for population pharmaceutical quality evaluation.A descriptive analysis method based on QbD concept was first established to characterize the process by critical evaluation attributes(CEAs).Then quantitative analysis method based on an improved statistical process control(SPC)method was established to investigate the process indicators(PIs)in the process population,such as mean distribution,batch-to-batch difference and abnormal quality probability.After that rules for risk assessment were established based on the SPC limitations and parameters.Both the SPC parameters of the CEAs and the risk of PIs were visualized according to the interaction test results to obtain a better understanding of the population pharmaceutical quality.Finally,an assessment strategy was built and applied to generic drug consistency assessment,process risk assessment and quality trend tracking.The strategy demonstrated in this study could help reveal quality consistency from the perspective of process control and process risk,and further show the recent development status of domestic pharmaceutical production processes.In addition,a process risk assessment and population quality trend tracking provide databased information for approval.Not only can this information serve as a further basis for decisionmaking by the regulatory authority regarding early warnings,but it can also reduce some avoidable adverse reactions.With continuous addition of data,dynamic population pharmaceutical quality is meaningful for emergencies and decision-making regarding drug regulation.展开更多
The study aims to prepare naproxen enteric-coated pellets(NAP-ECPs)by fluid-bed coating using QbD principle.Risk assessment was firstly performed by using failure mode and effect analysis(FMEA)methodology.A PlacketteB...The study aims to prepare naproxen enteric-coated pellets(NAP-ECPs)by fluid-bed coating using QbD principle.Risk assessment was firstly performed by using failure mode and effect analysis(FMEA)methodology.A PlacketteBurman design was then used for assessment of the most important variables affecting enteric-coated pellets characteristics.A BoxeBehnken design was subsequently used for investigating the main,interactive,and quadratic effects of these variables on the response.By FMEA we discovered that eight factors should be considered to be high/important risk variables as compared with others.The responses of acid resistance and cumulative drug release were taken as critical quality attributes(CQAs).Pareto ranking analyses indicated that the coating weight gain(X_(7)),triethyl citrate percentage(X_(1))and glycerol monostearate percentage(X_(2))were the most significant factors affecting the selected responses out of the eight high-risk variables.Optimization with response surface method(RSM)further fully clarified the relationship between X_(7),X_(1),X_(2) and CQAs,and design space was established based on the constraints set on the responses.Due to the extreme coincidence of the predicted value generated by model with the observed value,the accuracy and robustness of the model were confirmed.It could be concluded that a promising NAP-ECPs was successfully designed using QbD approach in a laboratory scale.展开更多
Objective This study aimed to design and optimize the water extraction process for Chuantieling(喘贴灵,CTL)based on the concept of quality by design(QbD).Methods The single-factor experiments were used to select the b...Objective This study aimed to design and optimize the water extraction process for Chuantieling(喘贴灵,CTL)based on the concept of quality by design(QbD).Methods The single-factor experiments were used to select the best experimental points of CTL water extraction.On this basis,the transfer rate of ephedrine hydrochloride and sin-apine thiocyanate,and the yield of the extract were evaluated as the evaluation indicators.The liquid-solid ratio,extraction time,and pH value were selected as the main factors to carry out the Box-Behnken design(BBD).A mathematical model of the critical process parameters(CPPs)and critical quality attributes(CQAs)was established,the interaction between CQAs and CPPs was examined,and the CTL extraction process design space was established and optimized,which guaranteed the stability of the process.The high performance liquid chro-matography(HPLC)was used to analyze the main active compounds in the CTL extract.Results Through single-factor experiments,the best experimental parameters were found to be a liquid-solid ratio of 8∶1,extraction time of 90 min,pH value of 4,and extraction times of three.The experimental variance analysis results of the BBD showed that the P value of the re-gression model was less than 0.05,and the lack-of-fit value was greater than 0.01,indicating that the constructed model had good predictive ability.The operating space of the CPPs of the CTL water extraction process was combined with the actual production situation.In the pro-duction situation,the best extraction process was nine times of water addition,72 min of ex-traction time,and 4.5 of pH value.The HPLC results showed that the peak areas of ephedrine hydrochloride,sinapine thiocyanate,tetrahydropalmatine,methyl eugenol,cinnamaldehyde,and 6-gingerol in the CTL extract accounted for 0.94%,14.32%,0.78%,31.23%,0.34%,and 0.44%of the total peak area,respectively.Conclusion The water extraction process design space of CTL based on QbD was conducive to actual production operations,ensuring the stability of the process.展开更多
Coptis chinensis(Huanglian) is a commonly used traditional Chinese medicine(TCM) herb and alkaloids are the most important chemical constituents in it. In the present study, an isocratic reverse phase high performance...Coptis chinensis(Huanglian) is a commonly used traditional Chinese medicine(TCM) herb and alkaloids are the most important chemical constituents in it. In the present study, an isocratic reverse phase high performance liquid chromatography(RP-HPLC) method allowing the separation of six alkaloids in Huanglian was for the first time developed under the quality by design(Qb D) principles. First, five chromatographic parameters were identified to construct a Plackett-Burman experimental design. The critical resolution, analysis time, and peak width were responses modeled by multivariate linear regression. The results showed that the percentage of acetonitrile, concentration of sodium dodecyl sulfate, and concentration of potassium phosphate monobasic were statistically significant parameters(P < 0.05). Then, the Box-Behnken experimental design was applied to further evaluate the interactions between the three parameters on selected responses. Full quadratic models were built and used to establish the analytical design space. Moreover, the reliability of design space was estimated by the Bayesian posterior predictive distribution. The optimal separation was predicted at 40% acetonitrile, 1.7 g·m L-1of sodium dodecyl sulfate and 0.03 mol·m L-1 of potassium phosphate monobasic. Finally, the accuracy profile methodology was used to validate the established HPLC method. The results demonstrated that the Qb D concept could be efficiently used to develop a robust RP-HPLC analytical method for Huanglian.展开更多
This paper focuses on a strategic improving quality of"high quality assurance CAE(computer aided engineering)analysis model"to be used in development design.The authors present a case oftransaxle oil seal le...This paper focuses on a strategic improving quality of"high quality assurance CAE(computer aided engineering)analysis model"to be used in development design.The authors present a case oftransaxle oil seal leakage in automotive drive trains,a technical reliability problem that generates bottlenecks for auto manufacturers around the world.The application of this model is used to analyze cavitation caused by the metal particles(foreign matter)generated through transaxle wear.This analyzing method primarily uses numerical simulation(CAE)to clarify the technological mechanism generating oil leaks as a result of foreign metallic substances entering oil seals in the drive train.Quality improvement using this CAE analyzing method was verified by successfully applying it to the technological problem of development design bottlenecks at auto manufacturers.展开更多
Places of large potentials of sustainable energy production and places of large energy consumption are often very different and separated by large distances across the globe. This paper first discusses potentials of s...Places of large potentials of sustainable energy production and places of large energy consumption are often very different and separated by large distances across the globe. This paper first discusses potentials of solar technology in terms of global availability using PV （photovoltaic） technology and actual energy production. Solar energy is widely under-used and one way to reduce this is to improve production in low-energy places with high demand： large cities. According to this option, about 40% of the electricity consumption in the built environment could be produced by solar PV systems and energy storage systems. This paper discusses conditions in the built environment and functional and design qualities enabling an increased diffusion of the technologies In a comparative analysis of PV technologies, the criteria taken into account encompass efficiency of the type of solar cell and commercial availability. Special attention is paid to the design features of different PV systems, like flexibility, colour and transparency that might help in their utilization as integrated in building material and ornaments in modem architecture. The same procedure is followed for electricity storage devices. The preliminary conclusion is that at present the freedom of design is largest for a combination of crystalline silicon PV cells and Li-ion batteries.展开更多
Mass movements are very common problems in the eastern Black Sea region of Turkey due to its climate conditions, geological, and geomorphological characteristics. High slope angle, weathering, dense rainfalls, and ant...Mass movements are very common problems in the eastern Black Sea region of Turkey due to its climate conditions, geological, and geomorphological characteristics. High slope angle, weathering, dense rainfalls, and anthropogenic impacts are generally reported as the most important triggering factors in the region. Following the portal slope excavations in the entrance section of Cankurtaran tunnel, located in the region, where the highly weathered andesitic tuff crops out, a circular toe failure occurred. The main target of the present study is to investigate the causes and occurrence mechanism of this failure and to determine the feasible remedial measures against it using finite element method(FEM) in four stages. These stages are slope stability analyses for pre-and postexcavation cases, and remediation design assessments for slope and tunnel. The results of the FEM-SSR analyses indicated that the insufficient initial support design and weathering of the andesitic tuffs are the main factors that caused the portal failure. After installing a rock retaining wall with jet grout columns and reinforced slope benching applications, the factor of safety increased from 0.83 to 2.80. In addition toslope stability evaluation, the Rock Mass Rating(RMR), Rock Mass Quality(Q) and New Austrian Tunneling Method(NATM) systems were also utilized as empirical methods to characterize the tunnel ground and to determine the tunnel support design. The performance of the suggested empirical support design, induced stress distributions and deformations were analyzed by means of numerical modelling. Finally, it was concluded that the recommended stabilization technique was essential for the dynamic long-term stability and prevents the effects of failure. Additionally, the FEM method gives useful and reasonably reliable results in evaluating the stability of cut slopes and tunnels excavated both in continuous and discontinuous rock masses.展开更多
The aim of this study is to identify and analyze ways to increase usage of destination website and motivate website visitors’intention to actually visit the destination.The sample population is South Koreans who visi...The aim of this study is to identify and analyze ways to increase usage of destination website and motivate website visitors’intention to actually visit the destination.The sample population is South Koreans who visit the VisitBritain website,the homepage of Britain’s national tourism agency.The data for this study were collected by a self-participated online survey on the blog of VisitBritain Korea,which is directly linked to the VisitBritain Korea website.Using structural equation modeling,six hypotheses were tested.The results show that the destination image on the destination marketing organization(DMO)website,quality of the destination website design including three dimensions(information quality,system quality,and service quality),and customers’satisfaction formed by high quality of the website design have a significant impact on website visitors’use intention and increase their visiting intention to the destination.Based upon the results of the analysis,managerial implications and areas for future research are proposed.展开更多
Objective:Quality by design integration is exceedingly imperative for industries dealing with pharmaceuticals,but it diminishes product variability and delivers an extraordinary degree of assurance that the product wo...Objective:Quality by design integration is exceedingly imperative for industries dealing with pharmaceuticals,but it diminishes product variability and delivers an extraordinary degree of assurance that the product would achieve the purpose for which it was formulated.The objective of the manuscript is to strengthen the understanding of the design of experimentation approach from the primary level.Hence,this review paper aims to get one experience with a course emphasizing product quality during its development process.Methods:The present work describes how experimental statistical designs can optimize the process.It is a strategy to improve the manufacturing of products and discuss the main factors involved in the production.The review describes different designs,advantages,disadvantages and design of experiments requirements concerning regulatory submissions.Results:Quality by design encourages the pharmaceutical industry to deal with risk management and proper understanding of products and manufacturing processes,assuring a good quality product.Having knowledge of quality by design and design of experiments in the formulation and process development will be beneficial for the optimization of drug delivery systems in upcoming times.Conclusion:Implementing quality by design at different phases in pharmaceutical manufacturing,the final product with a great degree of reproducible quality may be assured,depending upon experimental data.This contains valuable information in guiding new researchers about the importance and ways of using the design of experiments.展开更多
Understanding the mechanical properties of the lithologies is crucial to accurately determine the horizontal stress magnitude.To investigate the correlation between the rock mass properties and maximum horizontal stre...Understanding the mechanical properties of the lithologies is crucial to accurately determine the horizontal stress magnitude.To investigate the correlation between the rock mass properties and maximum horizontal stress,the three-dimensional(3D)stress tensors at 89 measuring points determined using an improved overcoring technique in nine mines in China were adopted,a newly defined characteristic parameter C_(ERP)was proposed as an indicator for evaluating the structural properties of rock masses,and a fuzzy relation matrix was established using the information distribution method.The results indicate that both the vertical stress and horizontal stress exhibit a good linear growth relationship with depth.There is no remarkable correlation between the elastic modulus,Poisson's ratio and depth,and the distribution of data points is scattered and messy.Moreover,there is no obvious relationship between the rock quality designation(RQD)and depth.The maximum horizontal stress σ_(H) is a function of rock properties,showing a certain linear relationship with the C_(ERP)at the same depth.In addition,the overall change trend of σ_(H) determined by the established fuzzy identification method is to increase with the increase of C_(ERP).The fuzzy identification method also demonstrates a relatively detailed local relationship betweenσ_H and C_(ERP),and the predicted curve rises in a fluctuating way,which is in accord well with the measured stress data.展开更多
The prediction of slope stability is a complex nonlinear problem.This paper proposes a new method based on the random forest(RF)algorithm to study the rocky slopes stability.Taking the Bukit Merah,Perak and Twin Peak(...The prediction of slope stability is a complex nonlinear problem.This paper proposes a new method based on the random forest(RF)algorithm to study the rocky slopes stability.Taking the Bukit Merah,Perak and Twin Peak(Kuala Lumpur)as the study area,the slope characteristics of geometrical parameters are obtained from a multidisciplinary approach(consisting of geological,geotechnical,and remote sensing analyses).18 factors,including rock strength,rock quality designation(RQD),joint spacing,continuity,openness,roughness,filling,weathering,water seepage,temperature,vegetation index,water index,and orientation,are selected to construct model input variables while the factor of safety(FOS)functions as an output.The area under the curve(AUC)value of the receiver operating characteristic(ROC)curve is obtained with precision and accuracy and used to analyse the predictive model ability.With a large training set and predicted parameters,an area under the ROC curve(the AUC)of 0.95 is achieved.A precision score of 0.88 is obtained,indicating that the model has a low false positive rate and correctly identifies a substantial number of true positives.The findings emphasise the importance of using a variety of terrain characteristics and different approaches to characterise the rock slope.展开更多
In the recent decades,effects of blast loads on natural and man-made structures have gained considerable attention due to increase in threat from various man-made activities.Site-specific empirical relationships for c...In the recent decades,effects of blast loads on natural and man-made structures have gained considerable attention due to increase in threat from various man-made activities.Site-specific empirical relationships for calculation of blast-induced vibration parameters like peak particle velocity(PPV)and peak particle displacement(PPD)are commonly used for estimation of blast loads in design.However,these relation-ships are not able to consider the variation in rock parameters and uncertainty of in situ conditions.In this paper,a total of 1089 published blast data of various researchers in different rock sites have been collected and used to propose generalized empirical model for PPV by considering the effects of rock parameters like unit weight,rock quality designation(ROD),geological strength index(GSI),and uniaxial compressive strength(UCS).The proposed PPV model has a good correlation coefficient and hence it can be directly used in prediction of blast-induced vibrations in rocks.Standard errors and coefficient of correlations of the predicted blast-induced vibration parameters are obtained with respect to the observed field data.The proposed empirical model for PPV has also been compared with the empirical models available for blast vibrations predictions given by other researchers and found to be in good agreement with specific cases.展开更多
In th is study, a n e w m odel w as p re se n te d for com p u tin g stre n g th o f rock m asses based u p o n in -situo bservations o f RQD p o pularly kno w n as rock quality d esignation. This m odel links u p th ...In th is study, a n e w m odel w as p re se n te d for com p u tin g stre n g th o f rock m asses based u p o n in -situo bservations o f RQD p o pularly kno w n as rock quality d esignation. This m odel links u p th e rock m assp aram eters from in -situ investigations w ith th e stre n g th p a ram eters o f jo in ted rocks obtain ed fromlaboratory scale ex p erim en tal observations. Using th e co n stitu tiv e relation, th e a u th o r derived a p ressu reand d am age sensitive plastic p a ra m e te r to d ete rm in e stre n g th o f rock m asses for varied ex te n ts ofd isco n tin u ity an d p ressu re induced dam age. The te s t results show th a t plasticity characterized byhard en in g an d softening inclusive o f dam ag e invariably d e p en d s u p o n m ean p ressu re an d e x te n t ofdefo rm atio n s alread y experien ced by rock m asses. The p re se n t w ork explores th e te s t d a ta th a t revealth e d ep en d en c e o f in -situ stren g th on increm ental jo in t p ara m e te rs o b tain ed from th e jo in t num ber,jo in t orien tatio n , jo in t roughness, gouge p a ram eters an d w a te r pressure. S ubstituting th e relationshipb e tw e e n th e RQD and m odified jo in t factor w ith th a t b e tw e e n m odulus ratio an d stren g th ratio, th em odel show s successfully th a t using d am age inclusive plastic p a ra m e te r an d RQD provides a relationshipfor estim atin g th e stre n g th o f rock m asses. One o f th e m ain objectives o f this w ork is to illustrate th a t th ep re se n t m odel is sensitive to p la s tic ity a n d dam ag e to g e th e r in estim atin g in -situ stre n g th o f rock m assesin foundations, u n d e rg ro u n d excavation an d tunnels.展开更多
The study focused on the fluid-bed granulation process of a product with two active pharmaceutical ingredients,intended for coated tablets preparation and further transfer to industrial scale.The work aimed to prove t...The study focused on the fluid-bed granulation process of a product with two active pharmaceutical ingredients,intended for coated tablets preparation and further transfer to industrial scale.The work aimed to prove that an accurate control of the critical granulation parameters can level the input material variability and offer a user-friendly process control strategy.Moreover,an in-line Near-Infrared monitoring method was developed,which offered a real time overview of the moisture level along the granulation process,thus a reliable supervision and control process analytical technology(PAT)tool.The experimental design’s results showed that the use of apparently interchangeable active pharmaceutical ingredients(APIs)and filler sorts that comply with pharmacopoeial specifications,lead to different end-product critical attributes.By adapting critical granulation parameters(i.e.binder spray rate and atomising pressure)as a function of material characteristics,led to granules with average sizes comprised in a narrow range of 280–320μm and low nongranulated fraction of under 5%.Therefore,the accurate control of process parameters according to the formulation particularities achieved the maintenance of product within the design space and removed material related variability.To complete the Quality by design(QbD)strategy,despite its limited spectral domain,the microNIR spectrometer was successfully used as a robust PAT monitoring tool that offered a real time overview of the moisture level and allowed the supervision and control of the granulation process.展开更多
Over the recent few decades,many groups of formulation scientists are concentrating on rapid release dosage forms in oral cavity.Among all fast release dosage forms,orodispersible films are successful to attract pharm...Over the recent few decades,many groups of formulation scientists are concentrating on rapid release dosage forms in oral cavity.Among all fast release dosage forms,orodispersible films are successful to attract pharmaceutical industry due to ease of formulation and extension patent life.Films are popular in patients too because of quick onset and user friendliness of dosage form.From the beginning,solvent casting has been selected as method of choice for manufacturing of orodispersible films.Solvent casting has been proved as a benchmark technology because of ease in product development,process optimization,process validation and technology transfer to production scale despite of some drawbacks like more number of unit operations involved and consumption of large quantity of solvents with controlled limits of organic volatile impurities in final formulation.The application of hot-melt extrusion(HME)in the pharmaceutical industry is consecutively increasing due to its proven innumerable advantages like solvent free continuous process with fewer unit operations and better content uniformity.Very few development activities has been initiated in the field of hot melt extruded orodispersible films so far.This extensive review covers detailed discussion of heavy duty industrial extruders,selection of downstream equipments,selection of excipients,common problems found in formulations and their remedies.Successive part of review addresses identification of critical quality attributes,quality target profile of product,criticality in selection of process parameters and material for substantial simulation in laboratory scale and production for successful technology transfer.展开更多
文摘Architectural design technology management covers multiple aspects,including the formulation of technical standards,method selection,etc.It plays a key role in design quality,such as establishing a closed-loop management mechanism for the entire process and utilizing BIM collaborative platforms.It also introduces the application of techniques such as parametric design and the construction of quality prediction models.Simultaneously elaborating on the formulation of enterprise standards and other related content,this paper finally proposes an integrated solution while pointing out development bottlenecks and prospects.
文摘Northwest Electric Power Design Institute (NWEPDI)was established in 1956. The institute undertakes the engineering exploration, survey and design of thermal electric power plant, conventional island of nuclear power plant, power transmission and substation projects, design of the 1st and 2nd class pressure vessels, electric power system planning, environmental protection engineering monitoring, assessment and design, various industrial and civil architectural design and the scicntific research and technical development tasks of corresponding specialities. The institute
基金Supported by Taishan Scholar Special Funding,No.tsqnz20240858Medical and Health Technology Project of Shandong Province,No.202402050122+4 种基金Science and Technology Development Plan of Jinan Municipal Health Commission,No.2024301008Clinical Medical Science and Technology Innovation Program of Jinan Science and Technology Bureau,No.202430055Natural Science Foundation of Jiangxi Province,No.20224BAB206077Gansu Provincial Hospital Intra-Hospital Research Fund Project,No.22GSSYB-6and the 2022 Master/Doctor/Postdoctoral Program of National Health Commission Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor,No.NHCDP2022004 and No.NHCDP2022008.
文摘Knee osteoarthritis(KOA),characterized by heterogeneous arthritic manifestations and complex peripheral joint disorder,is one of the leading causes of disability worldwide,which has become a high burden due to the multifactorial nature and the deficiency of available disease-modifying treatments.The application of mesenchymal stem/stromal cells(MSCs)as therapeutic drugs has provided novel treatment options for diverse degenerative and chronic diseases including KOA.However,the complexity and specificity of the“live”cells have posed challenges for MSC-based drug development and the concomitant scale-up preparation from laboratory to industrialization.For instance,despite the considerable progress in ex vivo cell culture technology for fulfilling the robust development of drug conversion and clinical trials,yet significant challenges remain in obtaining regulatory approvals.Thus,there’s an urgent need for the research and development of MSC drugs for KOA.In this review,we provide alternative solution strategies for the preparation of MSC drugs on the basis of the principle of quality by design,including designing the cell production processes,quality control,and clinical applications.In detail,we mainly focus on the quality by design method for MSC manufacturing in standard cell-culturing factories for the treatment of KOA by using the Quality Target Product Profile as a starting point to determine potential critical quality attributes and to establish relationships between critical material attributes and critical process parameters.Collectively,this review aims to meet product performance and robust process design,and should help to reduce the gap between compliant products and the production of compliant good manufacturing practice.
基金indebted to the Sohar University and the University of Buraimi, Oman, to support this study
文摘The assessment of in situ permeability of rock mass is challenging for large-scale projects such as reservoirs created by dams,where water tightness issues are of prime importance.The in situ permeability is strongly related to the frequency and distribution of discontinuities in the rock mass and quantified by rock quality designation(RQD).This paper analyzes the data of hydraulic conductivity and discontinuities sampled at different depths during the borehole investigations in the limestone and sandstone formations for the construction of hydraulic structures in Oman.Cores recovered from boreholes provide RQD data,and in situ Lugeon tests elucidate the permeability.A modern technique of multivariate adaptive regression splines(MARS)assisted in correlating permeability and RQD along with the depth.In situ permeability shows a declining trend with increasing RQD,and the depth of investigation is within 50 m.This type of relationship can be developed based on detailed initial investigations at the site where the hydraulic conductivity of discontinuous rocks is required to be delineated.The relationship can approximate the permeability by only measuring the RQD in later investigations on the same site,thus saving the time and cost of the site investigations.The applicability of the relationship developed in this study to another location requires a lithological similarity of the rock mass that can be verified through preliminary investigation at the site.
基金supports from the General Directorate of ETIMADEN enterprises during the field studies at Simav open pit mine。
文摘Rock quality designation(RQD)has been considered as a one-dimensional jointing degree property since it should be determined by measuring the core lengths obtained from drilling.Anisotropy index of jointing degree(AI_(jd))was formulated by Zheng et al.(2018)by considering maximum and minimum values of RQD for a jointed rock medium in three-dimensional space.In accordance with spacing terminology by ISRM(1981),defining the jointing degree for the rock masses composed of extremely closely spaced joints as well as for the rock masses including widely to extremely widely spaced joints is practically impossible because of the use of 10 cm as a threshold value in the conventional form of RQD.To overcome this limitation,theoretical RQD(TRQD_(t))introduced by Priest and Hudson(1976)can be taken into consideration only when the statistical distribution of discontinuity spacing has a negative exponential distribution.Anisotropy index of the jointing degree was improved using TRQD_(t) which was adjusted to wider joint spacing by considering Priest(1993)’s recommendation on the use of variable threshold value(t)in TRQD_(t) formulation.After applications of the improved anisotropy index of a jointing degree(AI'_(jd))to hypothetical jointed rock mass cases,the effect of persistency of joints on structural anisotropy of rock mass was introduced to the improved AI'_(jd) formulation by considering the ratings of persistency of joints as proposed by Bieniawski(1989)’s rock mass rating(RMR)classification.Two real cases were assessed in the stratified marl and the columnar basalt using the weighted anisotropy index of jointing degree(W_AI'_(jd)).A structural anisotropy classification was developed using the RQD classification proposed by Deere(1963).The proposed methodology is capable of defining the structural anisotropy of a rock mass including joint pattern from extremely closely to extremely widely spaced joints.
基金The National Major Scientific and Technological Special Project for‘Significant New Drugs Development’(Grant No.:2017ZX0901001-007)provides support for this study.
文摘From a regulatory perspective,drug quality consistency evaluation must concern different processes used for the same drug.In this study,an assessment strategy based on quality by design(QbD)was developed for population pharmaceutical quality evaluation.A descriptive analysis method based on QbD concept was first established to characterize the process by critical evaluation attributes(CEAs).Then quantitative analysis method based on an improved statistical process control(SPC)method was established to investigate the process indicators(PIs)in the process population,such as mean distribution,batch-to-batch difference and abnormal quality probability.After that rules for risk assessment were established based on the SPC limitations and parameters.Both the SPC parameters of the CEAs and the risk of PIs were visualized according to the interaction test results to obtain a better understanding of the population pharmaceutical quality.Finally,an assessment strategy was built and applied to generic drug consistency assessment,process risk assessment and quality trend tracking.The strategy demonstrated in this study could help reveal quality consistency from the perspective of process control and process risk,and further show the recent development status of domestic pharmaceutical production processes.In addition,a process risk assessment and population quality trend tracking provide databased information for approval.Not only can this information serve as a further basis for decisionmaking by the regulatory authority regarding early warnings,but it can also reduce some avoidable adverse reactions.With continuous addition of data,dynamic population pharmaceutical quality is meaningful for emergencies and decision-making regarding drug regulation.
基金This study is financially supported by the major project of National College Students Innovation Project for the R&D of Novel Drugs(No.J1030830).
文摘The study aims to prepare naproxen enteric-coated pellets(NAP-ECPs)by fluid-bed coating using QbD principle.Risk assessment was firstly performed by using failure mode and effect analysis(FMEA)methodology.A PlacketteBurman design was then used for assessment of the most important variables affecting enteric-coated pellets characteristics.A BoxeBehnken design was subsequently used for investigating the main,interactive,and quadratic effects of these variables on the response.By FMEA we discovered that eight factors should be considered to be high/important risk variables as compared with others.The responses of acid resistance and cumulative drug release were taken as critical quality attributes(CQAs).Pareto ranking analyses indicated that the coating weight gain(X_(7)),triethyl citrate percentage(X_(1))and glycerol monostearate percentage(X_(2))were the most significant factors affecting the selected responses out of the eight high-risk variables.Optimization with response surface method(RSM)further fully clarified the relationship between X_(7),X_(1),X_(2) and CQAs,and design space was established based on the constraints set on the responses.Due to the extreme coincidence of the predicted value generated by model with the observed value,the accuracy and robustness of the model were confirmed.It could be concluded that a promising NAP-ECPs was successfully designed using QbD approach in a laboratory scale.
基金Hunan University of Traditional Chinese Medicine Graduate Training Quality Engineering Project(2019CX57)the First-class Discipline Project on Chinese Pharmacology of Hunan University of Chinese Medicine (201803)。
文摘Objective This study aimed to design and optimize the water extraction process for Chuantieling(喘贴灵,CTL)based on the concept of quality by design(QbD).Methods The single-factor experiments were used to select the best experimental points of CTL water extraction.On this basis,the transfer rate of ephedrine hydrochloride and sin-apine thiocyanate,and the yield of the extract were evaluated as the evaluation indicators.The liquid-solid ratio,extraction time,and pH value were selected as the main factors to carry out the Box-Behnken design(BBD).A mathematical model of the critical process parameters(CPPs)and critical quality attributes(CQAs)was established,the interaction between CQAs and CPPs was examined,and the CTL extraction process design space was established and optimized,which guaranteed the stability of the process.The high performance liquid chro-matography(HPLC)was used to analyze the main active compounds in the CTL extract.Results Through single-factor experiments,the best experimental parameters were found to be a liquid-solid ratio of 8∶1,extraction time of 90 min,pH value of 4,and extraction times of three.The experimental variance analysis results of the BBD showed that the P value of the re-gression model was less than 0.05,and the lack-of-fit value was greater than 0.01,indicating that the constructed model had good predictive ability.The operating space of the CPPs of the CTL water extraction process was combined with the actual production situation.In the pro-duction situation,the best extraction process was nine times of water addition,72 min of ex-traction time,and 4.5 of pH value.The HPLC results showed that the peak areas of ephedrine hydrochloride,sinapine thiocyanate,tetrahydropalmatine,methyl eugenol,cinnamaldehyde,and 6-gingerol in the CTL extract accounted for 0.94%,14.32%,0.78%,31.23%,0.34%,and 0.44%of the total peak area,respectively.Conclusion The water extraction process design space of CTL based on QbD was conducive to actual production operations,ensuring the stability of the process.
基金supported by National Natural Science Foundation of China(No.81403112)Beijing Natural Science Foundation(No.7154217)+1 种基金Scientific Research Program of Beijing University of Chinese Medicine(No.2015-JYB-XS104)Special Program for Beijing Key Laboratory of Chinese Medicine Manufacturing Process Control and Quality Evaluation(No.Z151100001615065)
文摘Coptis chinensis(Huanglian) is a commonly used traditional Chinese medicine(TCM) herb and alkaloids are the most important chemical constituents in it. In the present study, an isocratic reverse phase high performance liquid chromatography(RP-HPLC) method allowing the separation of six alkaloids in Huanglian was for the first time developed under the quality by design(Qb D) principles. First, five chromatographic parameters were identified to construct a Plackett-Burman experimental design. The critical resolution, analysis time, and peak width were responses modeled by multivariate linear regression. The results showed that the percentage of acetonitrile, concentration of sodium dodecyl sulfate, and concentration of potassium phosphate monobasic were statistically significant parameters(P < 0.05). Then, the Box-Behnken experimental design was applied to further evaluate the interactions between the three parameters on selected responses. Full quadratic models were built and used to establish the analytical design space. Moreover, the reliability of design space was estimated by the Bayesian posterior predictive distribution. The optimal separation was predicted at 40% acetonitrile, 1.7 g·m L-1of sodium dodecyl sulfate and 0.03 mol·m L-1 of potassium phosphate monobasic. Finally, the accuracy profile methodology was used to validate the established HPLC method. The results demonstrated that the Qb D concept could be efficiently used to develop a robust RP-HPLC analytical method for Huanglian.
文摘This paper focuses on a strategic improving quality of"high quality assurance CAE(computer aided engineering)analysis model"to be used in development design.The authors present a case oftransaxle oil seal leakage in automotive drive trains,a technical reliability problem that generates bottlenecks for auto manufacturers around the world.The application of this model is used to analyze cavitation caused by the metal particles(foreign matter)generated through transaxle wear.This analyzing method primarily uses numerical simulation(CAE)to clarify the technological mechanism generating oil leaks as a result of foreign metallic substances entering oil seals in the drive train.Quality improvement using this CAE analyzing method was verified by successfully applying it to the technological problem of development design bottlenecks at auto manufacturers.
文摘Places of large potentials of sustainable energy production and places of large energy consumption are often very different and separated by large distances across the globe. This paper first discusses potentials of solar technology in terms of global availability using PV （photovoltaic） technology and actual energy production. Solar energy is widely under-used and one way to reduce this is to improve production in low-energy places with high demand： large cities. According to this option, about 40% of the electricity consumption in the built environment could be produced by solar PV systems and energy storage systems. This paper discusses conditions in the built environment and functional and design qualities enabling an increased diffusion of the technologies In a comparative analysis of PV technologies, the criteria taken into account encompass efficiency of the type of solar cell and commercial availability. Special attention is paid to the design features of different PV systems, like flexibility, colour and transparency that might help in their utilization as integrated in building material and ornaments in modem architecture. The same procedure is followed for electricity storage devices. The preliminary conclusion is that at present the freedom of design is largest for a combination of crystalline silicon PV cells and Li-ion batteries.
文摘Mass movements are very common problems in the eastern Black Sea region of Turkey due to its climate conditions, geological, and geomorphological characteristics. High slope angle, weathering, dense rainfalls, and anthropogenic impacts are generally reported as the most important triggering factors in the region. Following the portal slope excavations in the entrance section of Cankurtaran tunnel, located in the region, where the highly weathered andesitic tuff crops out, a circular toe failure occurred. The main target of the present study is to investigate the causes and occurrence mechanism of this failure and to determine the feasible remedial measures against it using finite element method(FEM) in four stages. These stages are slope stability analyses for pre-and postexcavation cases, and remediation design assessments for slope and tunnel. The results of the FEM-SSR analyses indicated that the insufficient initial support design and weathering of the andesitic tuffs are the main factors that caused the portal failure. After installing a rock retaining wall with jet grout columns and reinforced slope benching applications, the factor of safety increased from 0.83 to 2.80. In addition toslope stability evaluation, the Rock Mass Rating(RMR), Rock Mass Quality(Q) and New Austrian Tunneling Method(NATM) systems were also utilized as empirical methods to characterize the tunnel ground and to determine the tunnel support design. The performance of the suggested empirical support design, induced stress distributions and deformations were analyzed by means of numerical modelling. Finally, it was concluded that the recommended stabilization technique was essential for the dynamic long-term stability and prevents the effects of failure. Additionally, the FEM method gives useful and reasonably reliable results in evaluating the stability of cut slopes and tunnels excavated both in continuous and discontinuous rock masses.
文摘The aim of this study is to identify and analyze ways to increase usage of destination website and motivate website visitors’intention to actually visit the destination.The sample population is South Koreans who visit the VisitBritain website,the homepage of Britain’s national tourism agency.The data for this study were collected by a self-participated online survey on the blog of VisitBritain Korea,which is directly linked to the VisitBritain Korea website.Using structural equation modeling,six hypotheses were tested.The results show that the destination image on the destination marketing organization(DMO)website,quality of the destination website design including three dimensions(information quality,system quality,and service quality),and customers’satisfaction formed by high quality of the website design have a significant impact on website visitors’use intention and increase their visiting intention to the destination.Based upon the results of the analysis,managerial implications and areas for future research are proposed.
文摘Objective:Quality by design integration is exceedingly imperative for industries dealing with pharmaceuticals,but it diminishes product variability and delivers an extraordinary degree of assurance that the product would achieve the purpose for which it was formulated.The objective of the manuscript is to strengthen the understanding of the design of experimentation approach from the primary level.Hence,this review paper aims to get one experience with a course emphasizing product quality during its development process.Methods:The present work describes how experimental statistical designs can optimize the process.It is a strategy to improve the manufacturing of products and discuss the main factors involved in the production.The review describes different designs,advantages,disadvantages and design of experiments requirements concerning regulatory submissions.Results:Quality by design encourages the pharmaceutical industry to deal with risk management and proper understanding of products and manufacturing processes,assuring a good quality product.Having knowledge of quality by design and design of experiments in the formulation and process development will be beneficial for the optimization of drug delivery systems in upcoming times.Conclusion:Implementing quality by design at different phases in pharmaceutical manufacturing,the final product with a great degree of reproducible quality may be assured,depending upon experimental data.This contains valuable information in guiding new researchers about the importance and ways of using the design of experiments.
基金financially supported by the National Natural Science Foundation of China(No.52204084)the Open Research Fund of the State Key Laboratory of Coal Resources and safe Mining,CUMT,China(No.SKLCRSM 23KF004)+3 种基金the Interdisciplinary Research Project for Young Teachers of USTB(Fundamental Research Funds for the Central Universities),China(No.FRF-IDRY-GD22-002)the Fundamental Research Funds for the Central Universities and the Youth Teacher International Exchange and Growth Program,China(No.QNXM20220009)the National Key R&D Program of China(Nos.2022YFC2905600 and 2022 YFC3004601)the Science,Technology&Innovation Project of Xiongan New Area,China(No.2023XAGG0061)。
文摘Understanding the mechanical properties of the lithologies is crucial to accurately determine the horizontal stress magnitude.To investigate the correlation between the rock mass properties and maximum horizontal stress,the three-dimensional(3D)stress tensors at 89 measuring points determined using an improved overcoring technique in nine mines in China were adopted,a newly defined characteristic parameter C_(ERP)was proposed as an indicator for evaluating the structural properties of rock masses,and a fuzzy relation matrix was established using the information distribution method.The results indicate that both the vertical stress and horizontal stress exhibit a good linear growth relationship with depth.There is no remarkable correlation between the elastic modulus,Poisson's ratio and depth,and the distribution of data points is scattered and messy.Moreover,there is no obvious relationship between the rock quality designation(RQD)and depth.The maximum horizontal stress σ_(H) is a function of rock properties,showing a certain linear relationship with the C_(ERP)at the same depth.In addition,the overall change trend of σ_(H) determined by the established fuzzy identification method is to increase with the increase of C_(ERP).The fuzzy identification method also demonstrates a relatively detailed local relationship betweenσ_H and C_(ERP),and the predicted curve rises in a fluctuating way,which is in accord well with the measured stress data.
基金support in providing the data and the Universiti Teknologi Malaysia supported this work under UTM Flagship CoE/RG-Coe/RG 5.2:Evaluating Surface PGA with Global Ground Motion Site Response Analyses for the highest seismic activity location in Peninsular Malaysia(Q.J130000.5022.10G47)Universiti Teknologi Malaysia-Earthquake Hazard Assessment in Peninsular Malaysia Using Probabilistic Seismic Hazard Analysis(PSHA)Method(Q.J130000.21A2.06E9).
文摘The prediction of slope stability is a complex nonlinear problem.This paper proposes a new method based on the random forest(RF)algorithm to study the rocky slopes stability.Taking the Bukit Merah,Perak and Twin Peak(Kuala Lumpur)as the study area,the slope characteristics of geometrical parameters are obtained from a multidisciplinary approach(consisting of geological,geotechnical,and remote sensing analyses).18 factors,including rock strength,rock quality designation(RQD),joint spacing,continuity,openness,roughness,filling,weathering,water seepage,temperature,vegetation index,water index,and orientation,are selected to construct model input variables while the factor of safety(FOS)functions as an output.The area under the curve(AUC)value of the receiver operating characteristic(ROC)curve is obtained with precision and accuracy and used to analyse the predictive model ability.With a large training set and predicted parameters,an area under the ROC curve(the AUC)of 0.95 is achieved.A precision score of 0.88 is obtained,indicating that the model has a low false positive rate and correctly identifies a substantial number of true positives.The findings emphasise the importance of using a variety of terrain characteristics and different approaches to characterise the rock slope.
文摘In the recent decades,effects of blast loads on natural and man-made structures have gained considerable attention due to increase in threat from various man-made activities.Site-specific empirical relationships for calculation of blast-induced vibration parameters like peak particle velocity(PPV)and peak particle displacement(PPD)are commonly used for estimation of blast loads in design.However,these relation-ships are not able to consider the variation in rock parameters and uncertainty of in situ conditions.In this paper,a total of 1089 published blast data of various researchers in different rock sites have been collected and used to propose generalized empirical model for PPV by considering the effects of rock parameters like unit weight,rock quality designation(ROD),geological strength index(GSI),and uniaxial compressive strength(UCS).The proposed PPV model has a good correlation coefficient and hence it can be directly used in prediction of blast-induced vibrations in rocks.Standard errors and coefficient of correlations of the predicted blast-induced vibration parameters are obtained with respect to the observed field data.The proposed empirical model for PPV has also been compared with the empirical models available for blast vibrations predictions given by other researchers and found to be in good agreement with specific cases.
文摘In th is study, a n e w m odel w as p re se n te d for com p u tin g stre n g th o f rock m asses based u p o n in -situo bservations o f RQD p o pularly kno w n as rock quality d esignation. This m odel links u p th e rock m assp aram eters from in -situ investigations w ith th e stre n g th p a ram eters o f jo in ted rocks obtain ed fromlaboratory scale ex p erim en tal observations. Using th e co n stitu tiv e relation, th e a u th o r derived a p ressu reand d am age sensitive plastic p a ra m e te r to d ete rm in e stre n g th o f rock m asses for varied ex te n ts ofd isco n tin u ity an d p ressu re induced dam age. The te s t results show th a t plasticity characterized byhard en in g an d softening inclusive o f dam ag e invariably d e p en d s u p o n m ean p ressu re an d e x te n t ofdefo rm atio n s alread y experien ced by rock m asses. The p re se n t w ork explores th e te s t d a ta th a t revealth e d ep en d en c e o f in -situ stren g th on increm ental jo in t p ara m e te rs o b tain ed from th e jo in t num ber,jo in t orien tatio n , jo in t roughness, gouge p a ram eters an d w a te r pressure. S ubstituting th e relationshipb e tw e e n th e RQD and m odified jo in t factor w ith th a t b e tw e e n m odulus ratio an d stren g th ratio, th em odel show s successfully th a t using d am age inclusive plastic p a ra m e te r an d RQD provides a relationshipfor estim atin g th e stre n g th o f rock m asses. One o f th e m ain objectives o f this w ork is to illustrate th a t th ep re se n t m odel is sensitive to p la s tic ity a n d dam ag e to g e th e r in estim atin g in -situ stre n g th o f rock m assesin foundations, u n d e rg ro u n d excavation an d tunnels.
基金This work was supported by the Romanian National Authority for Scientific Research and Innovation,CNCS-UEFISCDI[project number PN-III-P2-2.1-BG-2016-0201].
文摘The study focused on the fluid-bed granulation process of a product with two active pharmaceutical ingredients,intended for coated tablets preparation and further transfer to industrial scale.The work aimed to prove that an accurate control of the critical granulation parameters can level the input material variability and offer a user-friendly process control strategy.Moreover,an in-line Near-Infrared monitoring method was developed,which offered a real time overview of the moisture level along the granulation process,thus a reliable supervision and control process analytical technology(PAT)tool.The experimental design’s results showed that the use of apparently interchangeable active pharmaceutical ingredients(APIs)and filler sorts that comply with pharmacopoeial specifications,lead to different end-product critical attributes.By adapting critical granulation parameters(i.e.binder spray rate and atomising pressure)as a function of material characteristics,led to granules with average sizes comprised in a narrow range of 280–320μm and low nongranulated fraction of under 5%.Therefore,the accurate control of process parameters according to the formulation particularities achieved the maintenance of product within the design space and removed material related variability.To complete the Quality by design(QbD)strategy,despite its limited spectral domain,the microNIR spectrometer was successfully used as a robust PAT monitoring tool that offered a real time overview of the moisture level and allowed the supervision and control of the granulation process.
文摘Over the recent few decades,many groups of formulation scientists are concentrating on rapid release dosage forms in oral cavity.Among all fast release dosage forms,orodispersible films are successful to attract pharmaceutical industry due to ease of formulation and extension patent life.Films are popular in patients too because of quick onset and user friendliness of dosage form.From the beginning,solvent casting has been selected as method of choice for manufacturing of orodispersible films.Solvent casting has been proved as a benchmark technology because of ease in product development,process optimization,process validation and technology transfer to production scale despite of some drawbacks like more number of unit operations involved and consumption of large quantity of solvents with controlled limits of organic volatile impurities in final formulation.The application of hot-melt extrusion(HME)in the pharmaceutical industry is consecutively increasing due to its proven innumerable advantages like solvent free continuous process with fewer unit operations and better content uniformity.Very few development activities has been initiated in the field of hot melt extruded orodispersible films so far.This extensive review covers detailed discussion of heavy duty industrial extruders,selection of downstream equipments,selection of excipients,common problems found in formulations and their remedies.Successive part of review addresses identification of critical quality attributes,quality target profile of product,criticality in selection of process parameters and material for substantial simulation in laboratory scale and production for successful technology transfer.
