A review of development methods and EOR technologies for carbonate reservoirs

Carbonate reservoirs worldwide are complex in structure,diverse in form,and highly heterogeneous.Based on these characteristics,the reservoir stimulation technologies and fluid flow characteristics of carbonate reservoirs are briefly described in this study.The development methods and EOR technologies of carbonate reservoirs are systematically summarized,the relevant mechanisms are analyzed,and the application status of oil fields is catalogued.The challenges in the development of carbonate reservoirs are discussed,and future research directions are explored.In the current development processes of carbonate reservoirs,water flooding and gas flooding remain the primary means but are often prone to channeling problems.Chemical flooding is an effective method of tertiary oil recovery,but the harsh formation conditions require high-performance chemical agents.The application of emerging technologies can enhance the oil recovery efficiency and environmental friendliness to a certain extent,which is welcome in hard-to-recover areas such as heavy oil reservoirs,but the economic cost is often high.In future research on EOR technologies,flow field control and flow channel plugging will be the potential directions of traditional development methods,and the application of nanoparticles will revolutionize the chemical EOR methods.On the basis of diversified reservoir stimulation,combined with a variety of modern data processing schemes,multichannel EOR technologies are being developed to realize the systematic,intelligent,and cost-effective development of carbonate reservoirs.

Oil oxidation in the whole temperature regions during oil reservoir air injection and development methods

The oil oxidation characteristics of the whole temperature regions from 30 ℃ to 600 ℃ during oil reservoir air injection were revealed by experiments. The whole oil oxidation temperature regions were divided into four different parts: dissolving and inflation region, low temperature oxidation region, medium temperature oxidation region and high temperature oxidation region. The reaction mechanisms of different regions were explained. Based on the oil oxidation characteristics and filed tests results, light oil reservoirs air injection development methods were divided into two types: oxygen-reducing air flooding and air flooding;heavy oil reservoirs air injection in-situ combustion development methods were divided into two types: medium temperature in-situ combustion and high temperature in-situ combustion. When the reservoir temperature is lower than 120 ℃, oxygen-reducing air flooding should be used for light oil reservoir development. When the reservoir temperature is higher than 120 ℃, air flooding method should be used for light oil reservoir development. For a normal heavy oil reservoir, when the combustion front temperature is lower than 400 ℃, the development method is medium temperature in-situ combustion. For a heavy oil reservoir with high oil resin and asphalting contents, when the combustion front temperature is higher than 450 ℃, the development method at this condition is high temperature in-situ combustion. Ten years field tests of air injection carried out by PetroChina proved that air has advantages in technical, economical and gas source aspects compared with other gas agents for oilfield gas injection development. Air injection development can be used in low/super-low permeability light oil reservoirs, medium and high permeability light oil reservoirs and heavy oil reservoirs. Air is a very promising gas flooding agent.

Analytical Method Development and Validation of Some Biosimilar Drugs by High Performance Thin Layer Chromatography

A simple and rapid HPTLC analytical method has been developed and validated for the determination of Etanercept and Filgrastim in pure form and in marketed formulation. Both the drugs were chromatographed on silica gel 60 F254s HPTLC plates, as stationary phase. The mobile phase optimized for Filgrastim and Etanercept was Water: n-butanol (7.5:2.5 v/v) and Isopropyl alcohol: water (6.5:4.5 v/v), respectively. The chromatogram obtained was scanned at 225 nm and 222 nm for filgrastim and etanercept which resulted in a retention factor of 0.45 ± 0.07 and 0.32 ± 0.03, respectively. The method was validated for parameters like linearity, accuracy, precision, specificity and robustness. Recovery studies were performed at three concentration levels, to demonstrate suitability, accuracy and precision of proposed method. Statistical analysis proved that the proposed method is accurate and reproducible with linearity in the range of 500 to 3000 ng/band for filgrastim and 200 to 1200 ng/band for etanercept. The limit of detection and limit of quantification for filgrastim was found to be 63.418 ng/band and 192.177 ng/band. For etanercept, LOD and LOQ were found to be 33.381 ng/band and 101.153 ng/band, respectively. The proposed method can be employed for the routine analysis of selected biosimilars.

Development of a rapid GC-FID method to simultaneously determine triethylamine, diisopropylamine, and 1,1,3,3-tetramethylguanidine residues in an active pharmaceutical ingredient

A rapid GC-FID method was developed to simultaneously determine residual levels of triethylamine(TEA), 1,1,3,3-tetramethylguanidine(TMG), and diisopropylamine(DIPA) in the synthetic route of an active pharmaceutical ingredient(API). Due to the severe absorption of amines on GC stationary phases,GC columns with various stationary phases were evaluated for optimal peak shape and reproducibility.The final conditions used the Agilent CP-Volamine column to resolve the three amines in 12 min. Various inlet liners were also screened to further improve the sensitivity of the analysis. The Restek Siltek~? liner was selected to achieve the desired detectability for the method. The quantitation limits were 4, 3, and 4 mg/mL for TEA, DIPA, and TMG in the presence of API, respectively. All three amines showed good linearity(r > 0.999) and recoveries(> 90%) over the concentration range of 3 to 16 mg/mL. The testing of residual amines was initially performed at the penultimate stage of the synthesis. However, this work demonstrates that TMG can act as a proton sponge to react with salicylic acid, the counter ion of the penultimate, to form a volatile component that elutes at a different retention time. Consequently, in the final method, these three amines were monitored in the final API to circumvent the matrix interference.Key parameters of the method were qualified per method validation requirements in ICH guidelines. The method was successfully applied for batch testing during development and implemented as an inprocess control procedure at manufacturing sites.

Quality Control of Tramadol in Kisangani: Development, Validation, and Application of a UV-Vis Spectroscopic Method

Context: Substandard and falsified medicines are circulating in low-income countries mostly without any control. We availed a simple and not expensive UV-Vis spectroscopic method to evaluate the quality of tramadol in Kisangani before and during the Covid-19 period. Methods: For the analytical quantitative method, an experimental design was applied to set up the optimal levels of the selected factors, namely, pH of dissolution medium, type of cuvette, and wavelength. Taking into account the capsule pharmaceutical formulation within 80 - 120 μg·mL-1 concentration range, we analyzed 89 tramadol samples from pharmacies and hospitals of the six Kisangani municipalities. Results: pH showed a significant effect on absorbance, whereas quartz cuvette and wavelength did not. A typical 100 μg·mL-1 tramadol solution gave an absorbance of 0.64 at 272 nm. Validation highlighted a matrix effect observed with a 6% bias. A correction factor of 0.9372 allowed to improve the accuracy profile, which were then totally included within the 10% acceptance limits. Quality control revealed that 25 samples out of 89 were not compliant in terms of manufacturing license, registration status in DRC and content as well. Conclusion: This study showed that the strengthening of analytical strategy in Kisangani is a need.

A Stability Indicating Reverse Phase-HPLC Method Development and Validation for the Estimation of Rucaparib in Bulk and Pharmaceutical Dosage Form

The research was carried out for establishing a new reverse phase-HPLC stability indicating method for the quantification of Rucaparib. The experiment was determined on Waters HPLC instrument using 996 photo-diode array detector. The separation was done by using symmetry C-18 ODS (25 cm × 0.46 cm internal diameter) 5 μm analytical column containing mobile phase of Phosphate buffer (0.02 M) and methanol [65:35% v/v] adjusted pH to 4.8 by adding dilute ortho phosphoric acid. The method was run at 1 ml·min-1 at 286 nm detection. The drug was eluted at 5.484 min. After developing the method, it was assured for the intended use by validation which was done according to ICH Q2B guidelines. The analytical parameters checked were linearity, accuracy, repeatability, intermediate precision, limit of detection, limit of quantitation, ruggedness and robustness. It was observed that the response of the detector was linear in the range of 6 - 14 μg/ml with correlation coefficient of 0.999. The results of all the parameters were found to be within the acceptance criteria. The stability indicating assay method was established by using the samples generated by forced degradation process. The forced degradation was carried out by subjecting the drug to acid, alkali, thermal, oxidative and photolytic degradation and the results showed that the degradation products were successfully separated from the drug. Hence, this can be applied perfectly later for the analysis of quality of the rucaparib drug.

Analytical Method Development and Validation of Filgrastim by UV and RP-UFLC Methods

The research work was carried out for establishing a new Ultra Violet (UV)— Visible spectroscopy and Reverse phase-Ultra Fast Liquid Chromatography (RP-UFLC) method for the analysis and quantification of a biosimilar drug, Filgrastim. Filgrastim or recombinant methionyl granulocyte colony stimulating factor (rGCSF) is a glycoprotein. It has a biological action essential for proliferation and differentiation of hematopoetic and progenitor cells. The UV and RP-UFLC work was carried on a Shimadzu UV1800 Spectrophotometer and Shimadzu Prominence LC-20AD UFLC systems, respectively. The λmax of filgrastim was found to be 215 nm. The correlation coefficient by UV spectroscopy was found to be 0.9994 for the concentration range of 1 to 3 μg/ml in double distilled water. The Reverse phase UFLC was done by using Phenomenex C4 (25 cm × 0.46 cm internal diameter) 15 μ, 300 A° analytical column. The optimized mobile phase for binary elution was Acetonitrile and double distilled water (80:20) with a flow rate of 1 ml/min. The retention time of drug was at 3.2 min. It was observed that the response of the detector was linear in the range of 5 - 15 μg/ml with correlation coefficient value of 0.999. After developing the methods, it was assured for the intended use by validation of the analytical parameters like linearity, accuracy, precision, limit of detection, limit of quantitation, ruggedness and robustness. The results of all the parameters for both the methods were found to be within the acceptance criteria as per the International Council for Harmonisation (ICH) guidelines.

A Stability Indicating Reverse Phase-HPLC Method Development and Validation for the Estimation of Bimatoprost 0.3% &Timolol 0.5% Pharmaceutical Ophthalmic Dosage Form

The research was carried out to establish a new reverse phase-HPLC stability indicating method for quantifying Bimatoprost & Timolol in ophthalmic solution. The experiment of Bimatoprost & Timolol in ophthalmic solution method development was determined on Waters HPLC instrument using a UV Detector. The separation was done by using L11, Zorbex SB phenyl (4.6 mm × 250 mm internal diameter) 5 μm analytical column, containing mobile phase of Phosphate buffer (0.02 M), methanol, and acetonitrile [50:30:20 % v/v]. The method was run at 1 ml·min-1 at 210 nm for Bimatoprost and 295 nm for Timolol for detection. The drug was eluted at 10.81 min for Bimatoprost and 3.77 min for Timolol. After developing the method, it was assured for the intended use by validation, which was done according to ICH Q2B guidelines. The analytical parameters checked were Specificity/Selectivity, linearity, Range, accuracy, ruggedness, and robustness. It was observed that the response of the detector was linear in the range of 6 - 18 μg/ml with a correlation coefficient of 0.999. The results of all the parameters were found to be within the acceptance criteria. The stability-indicating assay method was established by using the samples generated by the forced degradation process. The forced degradation was carried out by subjecting the drug to acid, alkali, thermal, oxidative, and photolytic degradation, and the results showed that the degradation products were successfully separated from the drug. Hence, this can be applied perfectly later for the quantitative analysis of Bimatoprost 0.3% + Timolol 0.5% Ophthalmic Solution drugs for pharmaceutical use. Currently, there is no official method for Bimatoprost & Timolol combination products in USP or BP. Available research work related to single Bimatoprost or Timolol products was not suitable for testing Bimatoprost and Timolol combination drugs. Additionally, there is no stability-indicating method to test Bimatoprost & Timolol combination products which insist us to do research and develop a new reverse phase-HPLC indicating method which will be faster and more accurate.

Effects of Different Enucleation Methods on Developmental Potency of Pig Handmade Clone Reconstructed Embryos

Effects of different enucleation methods on developmental potency of pig handmade clone(HMC)reconstructed embryo was investigated in the paper.We compared enucleation efficiency of blind cut method,first polar body(Pb1)positioning method and demecolcine(DM)assisted enucleation,as well as their effects on development of HMC reconstructed embryos.The results showed that overall enucleation efficiency of Pb1 positioning method was significantly higher than that of blind cut method(P<0.05).The protuberance rate and overall enucleation efficiency of 0.4μg/mL DM treated group for 60 min was significantly higher than that of other concentrations and time treatment groups(P<0.05).For effects on development of HMC reconstructed embryos,there was no significant difference between DM-assisted enucleation and Pb1 positioning method.In conclusion,appropriate addition of DM could enhance enucleation efficiency of HMC,which had no significant influence on developmental potency of reconstructed embryos.

SOME DEVELOPMENTS IN VISCOUS FLUID DYNAMICS AND ITS NUMERICAL METHODS

Viscous fluid flows contain abundant "physical phenomena and the viscous fluid dynamics is of wide applications in the fields of natural and engineering sciences. After the basic equations of viscousfluiddynamics (i.e., the Navier-Stokes equations) came out, one of the most important contributions to the discipline was the boundary layer (BL) theory and the BL equations presented by Prandtl

档案袋评价法在高校发展型资助育人机制中的应用

新时期高校资助工作理念从保障型向发展型转变是时代发展的必然趋势。但是,当前高校发展型资助育人工作存在育人理念的理解不够深入、育人机制不够完善、缺少有效的学生评价方法等问题。档案袋评价法作为较为成熟的评价方法,其区别于传统的量性评价,重视多元化、个性化及人的全面和谐发展,优势明显。为此,在分析学生发展中的需求后,将“档案袋评价法”引入高校发展型资助育人机制中,设计应用“发展型学生档案袋”,为提升家庭困难学生未来发展能力,完善资助育人机制提供了新的理论方向和实践路径。

算法素养的多维分级评价体系研究

[目的/意义]算法社会的发展在为生产生活带来便利的同时也引发了大量的算法问题,如算法歧视、算法操纵、算法伦理缺失等。算法问题的解决离不开算法生命周期中多方主体的共同努力,但对算法设计者、开发者、平台运营者、监管者和社会大众等各主体的算法能力要求并非完全一致。因此,对不同主体的算法素养评价需要适应不同的能力和评价目标。[方法/过程]本研究通过将皮亚杰认知阶段理论的时序阶段划分转化为算法素养评价的等级划分,结合IRT项目反应理论和熵权法,提出算法素养的多维分级评价体系。[结果/结论]通过融入评价等级机制实现评价目标的可调节性,同时以社会大众这一典型主体为例进行算法素养的多维分级评价。

The Effect of the MNRI Method on Neurotransmitter Biomarkers of Individuals with Neurodevelopmental Disorders

Introduction: The MNRI (Masgutova Neurosensorimotor Reflex Integration) method was developed in 1989 in Russia and has spread world-wide to treat individuals with certain types reflex development deficits, behavior disorders, disorders of speech or language development, and learning disabilities. MNRI is based on techniques called “repatterning” or remodulation, meaning re-education, recoding the reflex nerve pathways specific for dynamic and postural reflex schemes. Objectives: Repatterning activates the extra pyramidal nervous system responsible for automatic mechanisms and processes, the extension of links between neurons, the growth of neural nets, myelination, and the creation of new nerve routing. This potential result was tested utilizing urinary measurements of the following neurotransmitters: epinephrine, norepinephrine, dopamine, DOPAC, serotonin, 5-HIAA, glycine, taurine, GABA, glutamate, PEA, and histamine. Methods: Neurological impact of the Masgutova Neurosensorimotor Reflex Method on the magnitude of changes in neurotransmitters was assessed by an external controlled and double-blind method using patients from one of the four diagnosis groups: 1) global developmental disorders;2) cerebral palsy, Traumatic Brain Injury (TBI), Acute Brain Injury (ABI), and seizures;3) ADD/ADHD;and 4) anxiety disorders. Results: The post-MNRI results in participants show a tendency for regulation of the above neurotransmitters resulting in their calming down, decrease of hypervigilance, stress resilience increase, improvements in behavioral and emotional regulation, positive emotions, and cognitive processes control. Conclusion: The application of the Masgutova Neurosensorimotor Reflex Method as a therapy modality offers a novelty paradigm for the treatment using neuro- and immune-modulation technologies presenting a non-pharmaceutical approach, based on use of neurosensorimotor reflex circuit concept.

Empirical Research on the Developmental Status of Farmer Cooperatives' Function

In the paper, members in farmer cooperatives are selected as investigation subjects. By using fuzzy synthetic evaluation methods, functions of farmer cooperatives, which include six functions as follows: providing technology and information, marketing, processing and transportation, standardized services, and credit services and rights protection, are analyzed. The quantitative analysis is conducted on the developmental status of the functions of farmer cooperatives. The evaluation results are taken as evidence to anticipate the problems in the development of farmer cooperatives and then countermeasures are put forward, including intensifying the construction of actual functions of farmer cooperatives; contracting diversified credit and loan services; improving comprehensive strength of farmer cooperatives and taking the path of combining professional and comprehensive developmental paths. This study improves our knowledge on the development of farmer cooperatives and provides new insights to solve the problems that arise following the development.

Robustness Study and Superior Method Development and Validation for Analytical Assay Method of Atropine Sulfate in Pharmaceutical Ophthalmic Solution

Background: The robustness is a measurement of an analytical chemical method and its ability to contain unaffected by little with deliberate variation of analytical chemical method parameters. The analytical chemical method variation parameters are based on pH variability of buffer solution of mobile phase, organic ratio composition changes, stationary phase (column) manufacture, brand name and lot number variation;flow rate variation and temperature variation of chromatographic system. The analytical chemical method for assay of Atropine Sulfate conducted for robustness evaluation. The typical variation considered for mobile phase organic ratio change, change of pH, change of temperature, change of flow rate, change of column etc. Purpose: The aim of this study is to develop a cost effective, short run time and robust analytical chemical method for the assay quantification of Atropine in Pharmaceutical Ophthalmic Solution. This will help to make analytical decisions quickly for research and development scientists as well as will help with quality control product release for patient consumption. This analytical method will help to meet the market demand through quick quality control test of Atropine Ophthalmic Solution and it is very easy for maintaining (GDP) good documentation practices within the shortest period of time. Method: HPLC method has been selected for developing superior method to Compendial method. Both the compendial HPLC method and developed HPLC method was run into the same HPLC system to prove the superiority of developed method. Sensitivity, precision, reproducibility, accuracy parameters were considered for superiority of method. Mobile phase ratio change, pH of buffer solution, change of stationary phase temperature, change of flow rate and change of column were taken into consideration for robustness study of the developed method. Results: The limit of quantitation (LOQ) of developed method was much low than the compendial method. The % RSD for the six sample assay of developed method was 0.4% where the % RSD of the compendial method was 1.2%. The reproducibility between two analysts was 100.4% for developed method on the contrary the compendial method was 98.4%.

Quantitative division of succession and spatial patterns among different stand developmental stages in Changbai Mountains

Broadleaf-Korean pine forests exhibit high species richness and distinctive species composition, which are currently becoming more dominant among natural forests in Changbai Mountains of northeastern China. Understanding the ecological process of restored vegetation is quite important for ecosystem reconstruction. Distinguishing stand development stages and analyzing the dynamic spatial patterns could provide insights into significant community coexistence mechanisms. In the present study, eight permanent study areas were established according to the substituting space for time method in Changbai Mountains of north-eastern China. The optimal division method was used to quantify the successional series into different stand development stages, and the point pattern analysis method(L(r) function) was used to analyse the dynamic changes in spatial patterns and interspecific associations. Our results suggested that:(1) The stand development process was divided into five stages: the first three stages were poplar-birch secondary forests in different stages of recovery, the fourth stage was thespruce-fir mixed forest, and the last stage was the primary broadleaf-Korean pine forest;(2) The spatial pattern showed an aggregated distribution at a small scale and changed to a random distribution as the scale increased in poplar-birch secondary forests, but the spatial pattern appeared to be randomly distributed in spruce-fir mixed forest and broadleafKorean pine forest;(3) The interspecific associations between pioneer species and climax species changed from negative to positive among the different stand stages, and environmental resources were shared among these species. Interspecific differences in shade tolerance among the tree species were key determinants of forest dynamics and structure. Our study is vital to the understanding of the forest development;thus, the spatial change features should receive greater attention when forest management is being planned and restoration strategies are being developed for the Changbai Mountains.

A New and Enantioselective Chromatographic Method for Linagliptin on Amylose Coated Chiral Stationary Phase

A new and enantioselective liquid chromatographic method was developed for estimation of S-Linagliptin in Linagliptin (LINA) drug substances. The desired enantiomeric separation was achieved on Chiralpak AD-H (250*4.6 mm*5 μm) column with the mobile phase composition of ethanol, methanol and diethylamine in a ratio of 90:10:0.1 (v/v/v) with flow rate of 0.5 mL·min-1 and column oven temperature 30°C and the eluted compounds were monitored at 225 nm. In the proposed chiral method, USP resolutions between both the enantiomers were more than 5.0. Limit of detection and Limit of quantitation of S-LINA was found to be 0.03 μg·mL-1 and 0.10 μg·mL-1 respectively. Linearity study was conducted from LOQ to 150% and correlation coefficient found to be 0.9997. Accuracy was within the range of 98.6% to 101.5%. To prove selectivity power of the method specificity study was conducted by subjecting drug substance to acid, base, hydrolysis, oxidation and photolysis and ensured the peak purity of analyte in degraded samples. Moreover, the method has been fully validated as per ICH guidelines. The proposed method is precise, accurate, linear, rugged, robust and suitable for accurate quantification of S-LINA in LINA drug substance.

Validated Chiral Ultra Fast Liquid Chromatographic Method for Quantitative Analysis of Enantiomeric Vildagliptin

A rapid, accurate, and precise chiral Ultra fast liquid chromatography (UFLC) method was developed and validated for enantiomeric separation of racemic vildagliptin and S-vildagliptin according to the guidelines of the International Conference on Harmonization (ICH). The chiral chromatographic separation was achieved with a mobile phase consisting of 20 mM borax buffer (pH 9.0 ± 0.05), ACN, and 0.1% Triethylamine (50:50:0.1, v/v/v) at a flow rate of 1 ml/min using a chiralcel OD-RH column, tris(3,5-dimethyl phenyl carbamate) (250 mm × 4.6 mm, 5 μm) column. The UFLC analysis was monitored at 210 nm. The method showed good linearity with a regression coefficient (r2) of 0.999 in the range of 1 - 12 μg/ml for S-vilda. The detection limit (LOD), quantitation limit (LOQ), and the average percentage recovery for S-vilda were found to be 0.024, 0.075 μg/mL, and 99.19% to 100.4%, respectively. The percentages of relative standard deviation (% RSD) for intra- and inter-day precision were found to be 0.346% and 0.364%, respectively. The developed method proved to be reproducible as % RSD was <2% and it had robustness within the acceptable limit. The percentage purity of pharmaceutical preparations of S-vilda was found to be 99.19 w/w. The proposed chiral method can be put in application for the enantiomeric purity determination of S-vilda formulations.