Design Quality Is Essential to Excellent Project

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

Using multivariate adaptive regression splines to develop relationship between rock quality designation and permeability

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.

A novel approach to structural anisotropy classification for jointed rock masses using theoretical rock quality designation formulation adjusted to joint spacing

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.

A quality by design (QbD) case study on entericcoated pellets: Screening of critical variables and establishment of design space at laboratory scale

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.

A strategy for population pharmaceutical quality assessment based on quality by design

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.

Extraction process in Chuantieling(CTL) based on the quality by design(QbD) concept

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.

Analyzing Cavitation Caused by Metal Particles in the Transaxle： Application of High Quality Assurance CAE Analysis Model

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.

Diffusion of Solar Energy Use in the Built Environment Supported by New Design

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.

Geotechnical investigations and remediation design for failure of tunnel portal section： a case study in northern Turkey

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.

Factors Affecting DMO’s Website Use Intention, and Visiting Intention: A SEM Model on the Impact of E-Destination Image and DMO’s Website Design

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.

Design of experiments:how to develop and optimize drug delivery systems

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.

Growth behavior and resource potential evaluation of gas hydrate in core fractures in Qilian Mountain permafrost area, Qinghai-Tibet Plateau

The Qilian Mountain permafrost area located in the northern of Qinghai-Tibet Plateau is a favorable place for natural gas hydrate formation and enrichment,due to its well-developed fractures and abundant gas sources.Understanding the formation and distribution of multi-component gas hydrates in fractures is crucial in accurately evaluating the hydrate reservoir resources in this area.The hydrate formation experiments were carried out using the core samples drilled from hydrate-bearing sediments in Qilian Mountain permafrost area and the multi-component gas with similar composition to natural gas hydrates in Qilian Mountain permafrost area.The formation and distribution characteristics of multi-component gas hydrates in core samples were observed in situ by X-ray Computed Tomography(X-CT)under high pressure and low temperature conditions.Results show that hydrates are mainly formed and distributed in the fractures with good connectivity.The ratios of volume of hydrates formed in fractures to the volume of fractures are about 96.8%and 60.67%in two different core samples.This indicates that the fracture surface may act as a favorable reaction site for hydrate formation in core samples.Based on the field geological data and the experimental results,it is preliminarily estimated that the inventory of methane stored in the fractured gas hydrate in Qilian Mountain permafrost area is about 8.67×1013 m3,with a resource abundance of 8.67×108 m3/km2.This study demonstrates the great resource potential of fractured gas hydrate and also provides a new way to further understand the prospect of natural gas hydrate and other oil and gas resources in Qilian Mountain permafrost area.

Whole-process optimization for industrial production of glucosamine sulfate sodium chloride based on QbD concept

The double salt of glucosamine sulfate sodium chloride(glucosamine-SP) is an important pharmaceuticals ingredient for healing osteoarthritis. However, the study about its industrial production is rarely documented, let alone the optimization over the whole process to produce glucosamine-SP using glucosamine hydrochloride and anhydrous sodium sulfate as synthetic raw materials. In order to improve the production efficiency, this study screened the process parameters based on the concept of quality by design(QbD), optimized 13 operational parameters related to reaction and separation in the process, and finally proposed the mixed dropping process. The reaction conditions for the preparation of glucosamineSP were found as follows: the molar ratio of anhydrous sodium sulfate to glucosamine hydrochloride is 0.42, the mass ratio of water to glucosamine hydrochloride is is 2.0, the reaction temperature is 50 ℃ and the reaction time is 1 h. Through step-by-step scaling up following QbD, the mixed dropping process was successfully applied to achieve a trial production of 200 kg products satisfying national quality standards.In all, the results of this study have high technical value and guiding significance for the industrial mass production of glucosamine-SP.

Computing in-situ strength of rock masses based upon RQD and modified joint factor: Using pressure and damage sensitive constitutive relationship

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.

Fluidised bed granulation of two APIs:QbD approach and development of a NIR in-line monitoring method

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.

Hot melt extrusion:An industrially feasible approach for casting orodispersible film

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.

Determination of blast-induced ground vibration equations for rocks using mechanical and geological properties

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.

Integrated Geophysical and Geotechnical Investigations for Earth Dam along Dansak River, Upper Shemankar River Basin, Jos Plateau, Central Nigeria

A total of 60 VES （geo-electrical resistivity soundings） and ten exploratory core holes （boreholes） were carried out along the axis of a proposed earth dam site as part of an overall geotechnical investigation for the design and construction of an earth dam along Dansak River, Shemankar River Basin, Jos Plateau, Nigeria. The geophysical interpretation revealed four to five geo-electric layers corresponding to lithologic units （1） topsoil from 0-2 m with a resistivity value of 〈 100-320 ohm-m, （2） weathered/slightly weathered basalt fi＇om 0.6 m to 20 m characterized by resistivity value of 27-130 ohm-m, followed by （3） basalt/fractured basalts with resistivity value of 130-400 ohm-m and （4） the basement rocks with resistivity value 〉 320 ohm-m to 3,021 ohm-m. Exploratory borehole drilling encountered a series of lithologic units viz： overburden （clay, silt and sand） weathered basalt, slightly weathered basalt, fresh/fractured basalts, weathered migmatite and migmatites/migmatite gneiss. Exploratory core analysis in terms of CR （core recovery） and RQD （rock quality designation） revealed an average of 70%-90% and 75%-90%, respectively. Lugeon test gave Lugeon values of 1-5 for the ten core holes. However, fractures with Lugeon value from 〉 5-15 lugeon were encountered on borehole numbers BH 1, 7, 8, 9 and 10. Grouting is recommended to seal this shallow to medium depth （0-15 m） fractures to reduce or eliminate possible seepage when the dam is constructed. The rock mass index grading for the dam axis ranges from good to excellent.

The Contributions of Building Information Modelling to Sustainable Construction

Global concerns toward environmental issues have induced growing demand for new approaches in the construction because of its considerable impact on the environment and use of natural resources. Through using construction sustainability tools, methods and techniques, a greener design can be applied during various building phases. In this connection, it is argued that the analytical and integrated models applied by Building Information Modelling (BIM) may also facilitate this process to be performed more efficiently. BIM and construction sustainability are quite different initiatives, but both have received much attention in recent years in the architecture, engineering and construction (AEC) industry. A rigorous analysis of the interactions between them implies that a synergy exists which, if properly it is understood that can be helpful to reduce the environmental impacts of the AEC industry. A BIM-based design model can contribute to sustainability through its three main dimensions which are environmental, economic and social. In this paper, by reviewing the existing literature on BIM and construction sustainability and using a matrix to analyze construction sustainability dimensions and BIM functionalities a number of interactions have been discussed. It can be concluded that despite there are many improvements in implementation of BIM in environmental and economic aspects of sustainability, its potential impact on social dimension has not been explicitly explored hence further studies need to be undertaken in this area.

QbD Approach Method Development for Estimation of Dabigatran Etexilate along with Its Impurities and Identification of Degradants in Capsule Dosage Form

The concept of Quality by Design was demonstrated in the development of a stability-indicating assay and related substances method by HPLC for Dabigatran Etexilate Capsules dosage form. Method design, method evaluation, method control and life cycle management were explained by systematic flow chart. Analytical Target Product profile was defined. The method was developed using the Inertsil ODS-3V, 150 mm × 4.6 mm, 5 μm column using the gradient program with ammonium formate buffer as mobile phase A and acetonitrile as mobile phase B. Risk assessment was performed as part of method evaluation. Design of experiment tools was used to optimize the chromatographic conditions. A two-level Full Factorial Design along with Face Centered Central Composite design augmentation was employed and statistical analysis of the experimental data uncovered the significant influential of chromatographic factors. The design space and the contour plot suggest that the current center point parameters can be further modified, resulting in better acceptability of the response parameters. The performance of the optimized method was validated according to current ICH guidelines. Dabigatran Etexilate Capsules was subjected to various stress conditions like oxidative, acid, base, hydrolytic, thermal, humidity, and photolytic degradations and evaluated chromatograms at 220 nm. The degradation products were well separated from each other and main peak, demonstrating the stability-indicating power of the method. One of the major degradant impurities, which are forming in neutral hydrolysis stress condition, is isolated and characterized by using analytical techniques like IR, LC-MS and NMR. Degradation pathway for Dabigatran Etexilate was proposed based on forced degradation data along with reaction mechanism.