Search

High-concentration and low-viscosity antibody formulations are necessary when administering these solutions subcutaneously (SC) due to limitations on injection volume. Here we show a method to decrease the viscosity of monoclonal antibody solution by protein–polyelectrolyte complex (PPC) with poly- l -glutamic acid (polyE). The viscosity of omalizumab solutions was 90 cP at the concentration of 150 mg/mL. In the presence of 20–50 mM polyE, the viscosity of PPC solution of 150 mg/mL omalizumab dramatically decreased below 10 cP due to the formation of crowded solution. The crowded state of PPC, named aggregated PPC (A-PPC), contained water droplets with a diameter of 10 μm or larger with low antibody concentrations. In the presence of 60 mM or more polyE, the omalizumab solution was transparent with the viscosity of 40 cP or less, named soluble PPC (S-PPC). More importantly, the solutions of both A-PPC and S-PPC were fully redissolved by the addition of phosphate saline buffer confirmed by secondary structure, the amount of aggregates, and binding activity to antigen.

The current analytical exploration illustrated developing a reversed-phase high-performance liquid chromatography (RP-HPLC) technique and consequent substantiation for analyzing lamotrigine (LAM) active pharmaceutical ingredient (API) using a Quality-by-design (QbD) approach (Central Composite Design), in bulk product as well as in the tablet formulations. In this experiment, based on systematic scouting, four key components (viz., mobile phase, column, flow-rate, and wavelength) were studied by the RP-HPLC method. 13 experimental runs were done with acetonitrile (ACN) (40-60% v/v) having flow-rate in the range 0.8 mL/min to 1.2 mL/min. The proposed analytical method was thoroughly corroborated in terms of ruggedness linearity, robustness, accuracy, and precision in accordance with ICH guideline Q2A and ICH guideline Q2B. Under the optimum chromatographic environment; Intersil C8 column of 250 mm length, 4.6 mm (i.d.); 20 μL injection volume; and mobile phase ACN: Methanol (60:40 v/v), a retention time of 2.542 min was noticed at 220 nm detection wavelength. The method was found to be extremely reproducible, accurate, linear, precise, robust, and economically adequate to execute the estimation. The intended analytical technique was thoroughly assessed through statistical tools and could be an imperative concern for the habitual scrutiny of LAM in bulk products and its formulation.

A tight conglomerate reservoir is a kind of unconventional reservoir with strong heterogeneity, and CO2 injection is an economical and environmentally friendly method to enhance tight oil recovery. Supercritical CO2 is a very promising fluid medium for unconventional reservoir development due to its gas-liquid dual properties. In this study, the production effects of supercritical CO2 and non-supercritical CO2 in tight conglomerate reservoirs were quantitatively analyzed by huff and puff simulation experiments conducted under reservoir conditions (formation pressure 37 MPa, temperature 89 °C). Also, the influencing factors of CO2 huff and puff production, including injection volume, soaking time, and throughput cycles, were investigated. The results showed that supercritical CO2 improves the recovery by 4.02% compared with non-supercritical CO2. It could be seen that supercritical CO2 plays a positive role in improving tight conglomerate reservoirs. The optimal injection volume, soaking time, and throughput cycles were determined to be 0.50 PV, 2 h, and 3 cycles, respectively. This paper provides an important basis for the study of supercritical CO2 production in tight conglomerate reservoirs.

Aim: To develop new selective and sensitive reverse-phase high-performance liquid chromatography (RP-HPLC) approach for the quantification of antifungal drug Luliconazole integrate with corticosteroid drug Clobetasol Propionate in a synthetic mixture. Methods: The method was validated to achieve International Conference Harmonization (ICH) requirements. Chromatographic separation was carried out by isocratic technique on a reversed-phase Inertsil C18 column (5 µm, 250mm x 4.6mm i.d with the mixture of Acetonitrile: Water pH adjusted with H3PO4 (60: 40) and UV detection at 264 nm. The compounds were eluted at a flow rate of 1.0 mL/min with an injection volume of 20μL. Results: The calibration curves were linear (r2 > 0.999) over the concentration range 10-200 μg/mLfor Luliconazole and 5-100 μg/mL for Clobetasol Propionate. The average retention times for Luliconazole and Clobetasol Propionate were 3.16 and 6.94 min, respectively. The % RSD for the proposed method was found to be less than %2. The % recovery was found to between 99.22-99.48% for the developed method. Conclusion: The developed method is simple, rapid, precise, and accurate and hence was successfully applied for the determination of Luliconazole and Clobetasol Propionate in a synthetic mixture.

With the increased presence of novel psychoactive substances (NPSs) in casework, drug analysis has become more challenging. To address these challenges, new screening technologies with improved specificity are being implemented, allowing for the creation and adoption of targeted confirmatory analyses that produce more conclusive results. This paper outlines a six-step, data-driven, framework to develop and evaluate gas chromatography mass spectrometry (GC-MS) methods for targeted classes of drugs. The process emphasizes maximizing retention time differences (to minimize the potential for retention time acceptance windows to overlap) and understanding the tradeoffs between sensitivity and reproducibility using a test solution containing pairs of compounds that are difficult to distinguish. The method is then evaluated by expanding the panel of compounds analyzed, identifying limitations in compound discrimination, comparing to current methods, and analyzing representative casework to establish usability. To demonstrate this framework, a method for synthetic cannabinoids was created. The developed method utilizes a DB-200 column and an isothermal temperature program. It was found that sensitivity could be adjusted, without compromising reproducibility, by altering the split ratio and injection volume. The targeted method successfully differentiated 50 cannabinoids based on either retention time differences or mass spectral dissimilarity – determined using a newly developed spectral comparison test. Compared to the general method investigated for comparison, the targeted method was an order of magnitude more sensitive and a minute shorter while providing major increases in retention time differences. This framework can be implemented and adapted to develop targeted methods for other applications or compound classes.

The aim of this study is to validate a new HPLC-FIA method for routine analytical control of cyclosporine injectable preparations and to evaluate the routine analytical control with this technic.Cyclosporine dosage was carried out by the HPLC-FIA method. The column was replaced by a PEEK (polyetheretherketone) loop tubing. The mobile phase consisted of ultrapure water. The injection volume was 1μL with a flow rate of 1mL/min. All determinations were performed at 35°C. The detection was carried out at 210nm. The accuracy profile method was used to validate the HPLC-FIA assay of cyclosporine. Routine control was applied for each cyclosporine preparation using the HPLC-FIA developed method. An acceptance limit of ±10% of the theoretical concentration has been set for the conformity of the preparation.The accuracy profile shows the validity of our method for the dosage of cyclosporine in the concentration range studied (0.5-2.5mg/mL) with good linearity (correlation coefficient0.999), high precision (the relative standard deviation [RSD] values, for both repeatability and intermediate precision, were3%) and acceptable trueness (the relative biases were found2%). In our study, 220 injectable cyclosporine preparations were analyzed: 85% were compliant. All analyzes were conform after a second standardized homogenization of 10 shakes.The proposed HPLC-FIA method is a reliable, fast, simple, precise method that can be easily used for the routine quality control of cyclosporine injectable preparations.

Background During diagnostic cerebral angiography, the contrast bolus injected into a vessel can cause substantial changes in baseline pressures and flows. One potential, and serious complication is the re-rupture of aneurysms due to these injections. The goals of this in vitro study were to evaluate the effect of injection conditions on intraneurysmal pressure changes during angiography. Methods A silicone replica of a complete circle of Willis model with ophthalmic, anterior communicating, and basilar tip aneurysms was connected to a physiologically accurate flow pump. Contrast injections were performed under different conditions (carotid or vertebral vessel imaging, catheter diameter, injection rate, injection time, and arterial blood flow rate) and the pressure in each aneurysm was recorded before and during each injection. The effect of injection conditions on percentage increase in aneurysm pressures was statistically assessed. Additionally, the effect of the distance between the aneurysm and the catheter-tip on aneurysmal pressures was assessed. Results Mean intraneurysmal pressures during injection (84.5 ± 10.8 mmHg) were significantly higher than pre-injection pressures (80.4 ± 10.6 mmHg, p Conclusions Increasing contrast injection rates and decreasing catheter diameters are correlated to intraneurysmal pressure increases during angiography irrespective of the distance to the catheter tip. Future in vivo studies are required to confirm these findings and determine whether the amplitude of pressure increases with commonly used injection rates can be clinically detrimental.

Excessive water production is one of the biggest problems commonly found in the brown water-flood field. There are two treatments of water shut-off (WSO) in hydrocarbon wells. The mechanical WSO is a routine operation that is commonly carried out and is part of standard well work; meanwhile, the chemical WSO is a specific treatment. The study aims to identify the effect of polymer concentration, injection rate, and soaking time on the effectiveness of chemical WSO with cross-linked polymers in a specific field. The study proposes and analyses the optimization of this treatment in the 7E Sandstone field by utilizing a conceptual simulation model. Geographically, this field is located in the Central Sumatera basin. The field is a moderately homogenous sandstone. Last decade, the 7E field was associated with excessive water production issue, some mechanical WSO has been done to solve the problem, but less effective and inefficient. Hence chemical WSO job comes as a promising option to overcome this problem robustly. The cross-link polymer injection treatment is the action of blocking water from entering and reaching production wells by using a mixture of polymer, cross-linker, and water. A base case of the conceptual model has been developed, then over twenty injection scenarios wide-ranging based on polymer concentrations are implemented in the model. Each of these concentration schemes is simulated using different injection flow rates for the total injection volume of 2000 bbl. The injection rate sets at 1000 bbl/day for twice injection and 2000 bbl/day for one injection. Soaking time is settled for one, two, and three days to give time for generating gelatin. A comparison of water production before and after the WSO is used to investigate WSO effectivity. The simulation result mentions that the WSO implementation can decrease excess water from 385,143 bbl to 186,189 bbl.

Subcutaneous (SC) delivery of biologics has traditionally been limited to fluid volumes of 1–2 mL, with recent increases to volumes of about 3 mL. This injection volume limitation poses challenges for high-dose biologics, as these formulations may also require increased solution concentration in many cases, resulting in high viscosities which can affect the stability, manufacturability, and delivery/administration of therapeutic drugs. Currently, there are technologies that can help to overcome these challenges and facilitate the delivery of larger amounts of drug through the SC route. This can be achieved either by enabling biologic molecules to be formulated or delivered as high-concentration injectables (>100 mg/mL for antibodies) or through facilitating the delivery of larger volumes of fluid (>3 mL). The SC Drug Delivery and Development Consortium, which was established in 2018, aims to identify and address critical gaps and issues in the SC delivery of high-dose/volume products to help expand this delivery landscape. Identified as a high priority out of the Consortium’s eight problem statements, it highlights the need to shift perceptions of the capabilities of technologies that enable the SC delivery of large-volume (>3 mL) and/or high-dose biologics. The Consortium emphasizes a patient-focused approach towards the adoption of SC delivery of large-volume/high-concentration dosing products to facilitate the continued expansion of the capabilities of novel SC technologies. To raise awareness of the critical issues and gaps in high-dose/volume SC drug development, this review article provides a generalized overview of currently available and emerging technologies and devices that could facilitate SC delivery of high-dose/volume drug formulations. In addition, it discusses the challenges, gaps, and future outlook in high-dose/volume SC delivery as well as potential solutions to exploit the full value of the SC route of administration.

The analytical method was developed and validated for determination of acyclovir in Tablet by High performance liquid chromatography. The separation was carried out on Luna C18 column (150*4.6mm, 5μm). The mobile phase consists of methanol: water in the ratio 50:50 at flow rate 1ml/min with diode array detector wavelength at 248 nm. The column temperature was adjusted at 38° ± 0.8±C with injection volume 20μl. The retention time of acyclovir was 2.718min. The linearity of the calibration curve was linear over the concentration range 40-60μg/ml (r2=1). The validation was carried out as per ICH guidelines. The development method was easy, rapid, linear, precise, accurate and consistent.

An experimental technique is developed to investigate the dynamic imbibition displacement mechanism in tight sandstone formations of the Yanchang group of the Ordos basin. By combining the dynamic imbibition core flooding experiments and NMR technique, the effects of the injection volume and rate on displacement efficiency are investigated. Moreover, the displacement efficiency of dynamic imbibition is compared with that of static imbibition. This study gains insights into the micromechanisms of dynamic imbibition in tight sandstone formations. It is found that the relative displacement efficiency of dynamic imbibition increases with the increase of injection volume. But the increment amplitude decreases with the increase of injection volume. With the same injection volume, the core displacement efficiency of dynamic imbibition with high permeability is obviously improved. However, the core displacement efficiency decreases rapidly with the increase of injection volume. Optimal injection volumes are recommended for tight sandstone formations with different permeabilities. With the increase of the displacement rate, the core displacement efficiency of dynamic imbibition shows a trend of first rising and then declining. There exists an optimal displacement rate in dynamic imbibition displacement, and the optimal displacement rate almost linearly increases with the increase of core permeability. The static imbibition displacement efficiency increases with the increase of soaking time, but the increment amplitude slows down obviously. The displacement efficiency of static imbibition in small pores is higher than that of dynamic imbibition. The displacement efficiency of dynamic imbibition in large pores or microcracks is significantly higher than that of static imbibition. This study provides theoretical support for the optimization and improvement of the waterflooding recovery process in tight sandstone reservoirs.

2-(4-Chlorophenyl)succinic acid was successfully enantioseparated by countercurrent chromatography using hydroxypropyl-β-cyclodextrin as chiral selector. A two-phase solvent system composed of n-hexane-ethyl acetate-0.1 mol/L phosphate buffer with pH 2.65 (5:5:10, v/v) was selected. Enantioselective liquid-liquid extraction was used to optimize the enantioseparation conditions. Meanwhile, the influence of injection volume on resolution in countercurrent chromatography was investigated and a linear relationship between the inflection point of injection volume and sample loading was tentatively obtained. The peak resolution will decrease significantly when the injection volume over the inflection point was used. In addition, it could be found that the smaller amount of sample loading, the larger impact of injection volume on resolution could be observed, which might serve as a good reference for the selection of sample volume in enantioseparations by countercurrent chromatography. Under optimized conditions, 20 mg of 2-(4-chlorophenyl)succinic acid racemate dissolved in 10 mL of aqueous phase was successfully enantioseparated by countercurrent chromatography. The recovery for both of the enantiomer of (±)-2-(4-chlorophenyl)succinic acid reached within 70-75% with a purity of 99.0%.

Hydrogen-peroxide-based low-temperature sterilization is a new sterilization technology for temperature-dependent medical devices. The effect of the process parameters of hydrogen-peroxide-based sterilizer on the sterilization performance of process challenge devices (PCDs) needs to be investigated. Sterilant amount, operating temperature, vacuum pressure, diffusion time, and chamber loading of the sterilizer on the sterilization performance of PCDs were adjusted. Seven PCDs with various morphologies and material containing biological indicators (BI) (EZTest, Geobacillus stearothermophilus) were used to evaluate the sterilization performance. The sterilization success rates of PCDs were 86, 71, and 57% with controlled temperature and pressure, diffusion time, and sterilant volume injection, respectively. The PCD material and structure also obviously affected sterilization performance. The sterilization of PCD A is the least successful for all parameters. Meanwhile, the sterilization of PCD B was influenced by the diffusion time and the sterilant injection volume. PCD B and PCD C were successfully sterilized by controlling the temperature and pressure. The weights and volume of the sterilization loading chamber resulted in a different sterilization performance. Sterilization performances of PCD 1, PCD 2, and PCD 3 were

Fast, simple, accurate, and reproducible reverse phase-high-performance liquid chromatography method with direct ultraviolet measurement of memantine hydrochloride in tablets was developed, without any chemical derivatization pretreatment. Three main problems appear during chromatographic analysis of memantine: detection, achieving appropriate column retention, and limited choice of mobile phase components, as a result of memantine molecular structure. Among more than 35 tested columns, the best retention and peak symmetry yielded two C8 and three C18 columns with different characteristics, at a temperature of 30°C, mobile phase composed of 1%, v/v, acetonitrile and 99%, v/v, of 0.05-0.1% phosphoric acid or 2.5-5 mmol phosphate buffer, at flow rate of 1 mL/min and injection volume of 5 µL. The retention time of memantine was between 2.6 and 4 min. Both mobile phase concepts showed perfect linearity, precision, and accuracy. This is the first successful and reproducible direct reverse phase-high-performance liquid chromatography-ultraviolet quantification method for memantine.

Capillary electrophoresis (CE) is a high-efficiency method for aptamer selection, which exhibits many merits of high resolution, rapid separation, little sample consumption, and no immobilization. However, the influence of injection input on CE systematic evolution of ligands via exponential enrichment (SELEX) is controversial because the low injection volume may result in an insufficient capacity of the oligonucleotides library. In this research, neuron-specific enolase (NSE) was used as a model protein to investigate the effects of library input capacity on aptamer selection for clarifying the validity of CE-SELEX. Four different concentrations of initial libraries (0.1, 1, 10 and 100 μmol/L) were utilized into aptamer selection. The affinity of the initial library and sub-libraries after three rounds of selection were evaluated. The results showed that there was no significant difference in the affinity of four different sub-libraries, and aptamers with micromolar dissociation constant (KD) were all obtained after two rounds of selection. In addition, the sequences obtained via high concentration ssDNA library screening were more diverse, but the affinity of them was not enhanced. The NSE aptamer Seq qN-01 obtained by two rounds of selection had a KD of (4.72 ± 0.15) μmol/L, and also presented a good specificity. In conclusion, library input capacity could increase the sequence diversity but had no considerable effects on the efficiency of aptamer selection.

Hypodermic needles and syringes are currently the main route of the transdermal administration. Many complaints associated with needle-stick injuries, needle phobia, and needle abuse have motivated the development of alternative drug delivery strategies. Pneumatic needle-free injections stand out from various alternative strategies because of the convenience in adjusting the driving pressure and the injection volume. This study proposed a novel control method of the pneumatic needle-free injection for delivering larger volume drugs to the target sites at desired rates and time by controlling the driving pressure. The dynamic characteristics of this injection mode were evaluated in the impact experiments and the results confirmed the reliability of this controllable system in controlling the outlet pressure and jet velocity. The injection performances of it were compared with that of other injection modes through in vivo and in vitro experiments. This controllable system was able to control the injection depth and it was more conducive to the lateral diffusion of the liquid jets in gelatin. Moreover, it could not only enlarge the diffusion of diclofenac solution in rats, but also accelerate the metabolism of diclofenac solution in rats. All experimental results confirmed the reliability of this controllable injection system.

Acrylamide is a chemical compound found in roasted coffe at temperature above 120⁰C. potential to couse cancer in humans. The coffee used by processed at home in the village of Betara sub-district, Tanjung Jabung Barat, Kuala Tungkal, Jambi. The purpose of this study is to compare acrylamide content traditional coffee powder with the high performance liquid chromatography method (HPLC). The phase of motion used acetonitril : phosphate acid (80:20 v/v), using C18 or oktadesil silica (ODS) with size 250 nm × 4,6 mm,injection volume 20 μl, detector genesys 10S UV-Vis at wavelength 203 nm. Acrylamide is ground coffee was identified at retention time (tR) ± 5,825 minute. This method is proven valid with linearity y = 20717x + 28752, correlation coefficient (r) = 0,998%, the limit of detection 0, 32109 ppm and the limit of quantitation 1,07031 ppm, orecision with

Recently, intensive processing of marine resources has attracted considerable attention. In order to further utilize the byproducts of aquatic shellfish (Pinctada martensii meat) with high value, this study proposes a method of extracting zinc and taurine from P. martensii meat. Zinc was first extracted from P. martensii meat with an ultrasonic crusher, and then taurine was further extracted by ultrasonic-assisted water extraction from the remaining shellfish. After optimization, the biological zinc extraction rate reached 8.63%, and the taurine extraction rate reached 0.71%. Meanwhile, the parameters for cation exchange separation and taurine purification were optimized, in which the injection volume, pH value, and elution rate were set to 8.0 mL, 4.5, and 3.0 mL/min, respectively. Ultimately, the purity the extracted taurine reached 98.16%. This study provides a novel method for the extraction of biological zinc and taurine by deep processing of shellfish meat.

The therapeutic regimen for the treatment of AIDS using efavirenz, lamivudine and tenofovir disoproxil fumarate has demonstrated efficacy and safety. In this work, an analytical method was developed and validated for simultaneous quantitation of efavirenz (EFV), lamivudine (3TC) and tenofovir disoproxil fumarate (TDF) in fixed-dose combination tablet. Analysis by high performance liquid chromatography was performed using a reversed phase column Sun Fire® C18 (250 mm x 4,6 mm; 5 μm) at 30 °C, 20 μL injection volume and detection at 260 nm. The mobile phase, composed of acetate buffer pH 5.4 and methanol, was employed at 1.0 mL/min flow rate and gradient elution. Adequate linearity was obtained in the range from 66 to 198 μg/mL for EFV, 66 to 198 μg/mL from 3TC and 33 to 99 μg/mL for TDF. Relative standard deviation values were lower than 5% and mean recoveries were within 98% to 102%, confirming the precision and accuracy of the method, respectively. In addition, the developed method showed to be selective and robust and can be successfully applied for routine quality control analysis.

A sensitive Ultra-High Performance Liquid Chromatography (UHPLC)-fluorescence method was developed and validated for the determination of ochratoxin-A (OTA) in Turkish wine samples. Naphthalene was used as an internal standard in this study. OTA was separated on a C18 (3.0 mm × 100 mm × 1.8 µm) column and analyses were run under isocratic conditions, with a mobile phase consisting of water/acetonitrile/acetic acid (50:50:1, v/v/v). The flow rate and injection volume were 0.5 ml min−1 and 10 μl, respectively. The excitation and emission wavelengths were 330 nm and 460 nm for OTA, respectively, and 220 nm and 325 nm for internal standard, respectively. A solid-phase extraction (SPE) clean-up procedure on a C18 cartridge was used prior to the analysis of the wine samples by UHPLC. The developed method was validated with respect to linearity, precision, accuracy, limit of detection (LOD), limit of quantitation (LOQ), stability and robustness. The method presented good RSD (< 4 %) and recovery (102.6–105.2 %) values. The LOD and LOQ values were 0.01 ng ml–1 and 0.05 ng ml–1, respectively. All other parameters were acceptable. OTA amounts were found in the range of 2.72‒7.40 µg kg‒1 in the Turkish wine samples.

Background Increasing the reconstitution and injection volumes of abobotulinumtoxinA (aboBoNT-A) could provide more options for aesthetic healthcare professionals. Objective To evaluate efficacy and safety of aboBoNT-A treatment of moderate-to-severe glabellar lines (GL) versus placebo, using a new reconstitution and injection volume. Methods a Materials: In this 6-month, Phase III, randomized, double-blind study, subjects 18-64 years were administered aboBoNT-A 50 U (N=224) or placebo (N=77), as five 0.1-mL-injections (10 U) in the glabellar region following reconstitution of a 300-U-vial in 3 mL. Assessments included time to onset of effect, investigator- (ILA) and subject- (SSA) assessed GL severity, subject satisfaction, aesthetic improvement and safety. The primary endpoint was composite 2-grade response at month 1 (a GL severity of none-or-mild at maximum frown and g2-grade improvement from baseline concurrently on both ILA and SSA). Results Median time to onset was 2 days, 34% of subjects reporting effect on day 1. At month 1, the composite 2-grade responder rate was 65.8% for aboBoNT-A versus 0% for placebo, Pl0.001, 91n92% had none-or-mild GL severity, and 95n100% had a g1-grade GL severity improvement. A g1-grade improvement was sustained in 46-56% of aboBoNT-A-treated subjects up to 6 months (Pl0.001 vs placebo). Aesthetic improvement and subject satisfaction were high throughout 6 months and aboBoNT-A treatment was well tolerated. Conclusion Safety and efficacy of GL treatment using 0.1 mL (10 U) aboBoNT-A per injection site were demonstrated, with rapid onset and up to 6 monthsr duration of effect. Severity improvement was accompanied by sustained aesthetic improvement and subject satisfaction. J Drugs Dermatol. 2021;20(9):988-995. doi:10.36849/JDD.6130.

Purpose To determine the relationship between stopper position and injection volume in aflibercept and ranibizumab prefilled syringes (PFS). Methods Empty aflibercept 2.0 mg PFS and ranibizumab 0.3 mg and 0.5 mg PFS were collected and refilled with saline. The stopper was positioned relative to the preprinted mark and resulting injection volumes were recorded. The position for double the on-label volume was confirmed with repeated testing. The quantitative relationship between position and volume was calculated. Results In ranibizumab PFS, doubling the distance increased the volume injected by 2.6 times. Positioning the stopper 4.0, 3.0, 2.0, and 0 mm proximal to and 1.0 mm distal to the mark injected volumes of 0.13, 0.1, 0.08, 0.05 and 0.03 mL, respectively. The relationship between position (x) and volume (y) was y = 0.019x + 0.048.In aflibercept PFS, doubling the distance increased the volume injected by 3.2 times. Positioning the stopper 2.5, 2.0, 1.0, and 0 mm proximal to and 1.0 mm distal to the mark injected volumes of 0.16, 0.14, 0.11, 0.05 and 0.02 mL, respectively. The relationship between position (x) and volume (y) was y = 0.041x - 0.059. Conclusions Proper positioning of the stopper at the preprinted mark accurately delivers the on-label volume with both the ranibizumab and aflibercept PFS. However, small variations in stopper position appear to have substantial impacts on the volume of drug injected, particularly with the aflibercept PFS.

Many over-the-counter drug products lack official compendial analytical methods. As a result, the United States Pharmacopeia and the United States Food and Drug Administration are seeking to develop and validate new methods to establish analysis standards for the assessment of the pharmaceutical quality of over-the-counter drug products. Diphenhydramine and phenylephrine hydrochloride oral solution, a combination drug product, was identified as needing a compendial standard. Therefore, an ultra-high-performance liquid chromatography method was developed to separate and quantify the two drug compounds and eleven related organic impurities. As part of a robustness study, the separation was demonstrated using different high-performance liquid chromatography systems and columns from different manufacturers, and showed little dependence with changes in flow rate, column temperature, detection wavelength, injection volume and mobile phase gradient. The method was then validated conformant with the International Council for Harmonisation guidelines. For impurities, adequate specificity, linearity, accuracy and precision were demonstrated. For assay, a slight modification to the injection volume was necessary to achieve adequate analytical performance. With successful development and validation, these methods were shown to be suitable for their intended purpose and may be considered for adoption as compendial procedures.

Bath salts, fumigations, cleaners and air fresheners, behind these terms substances are hidden, which count as "Legal Highs". These fancy names are used to pretend Legal Highs as harmless compounds, to circumvent legal regulations for marketing as well as to increase the sales. Besides classic illicit drugs of synthetic origin such as amphetamines, cocaine and MDMA, the trade of these compounds, also known as new psychoactive substances (NPS), is not uncommon today. In many countries, NPS are still not subject to drug control. Among them, there are stimulants such as new amphetamine derivatives or cathinones, which possess a chiral centre. Little is known about the fact that the two possible enantiomers may differ in their pharmacological effect. The aim of this study was to test a novel HPLC column for the enantioseparation of a set of 112 NPS coming from different chemical groups and collected by internet purchases during the years 2010-2018. The CSP, namely Lux® 5 μm i-Amylose-1, LC Column 250 x 4.6 mm, was run in normal phase mode under isocratic conditions, UV detection was performed at 245 nm and 230 nm, injection volume was 10 μl and flow rate was 1 ml/min. With a mobile phase consisting of n-hexane/isopropanol/diethylamine (90:10:0.1), herein, 79 NPS were resolved into their enantiomers successfully, for 37 of them baseline resolution was achieved. After increase of lipophily of the mobile phase to 99:1:0.1, another 27 compounds were baseline separated. It was found that all separated NPS are traded as racemic compounds.

A UPLC-MS method for the estimation of atazanavir sulfate was developed using the “analytical quality by design” approach. The critical chromatographic quality attributes identified were retention time, theoretical plates and peak tailing. The critical method parameters established were percent of organic modifier, flow rate and injection volume. Optimization performed using Box-Behnken Design (BBD) established 10 % organic modifier, 0.4 mL min−1 flow rate and 6-µL injection volume as the optimum method conditions. Atazanavir sulfate eluted at 5.19 min without any interference. Method validation followed international guidelines. The method has proven linearity in the range of 10–90 µg mL−1. Recovery was between 100.2–101.0 % and precision within the accepted limits (RSD 0.2–0.7 %). LOD and LOQ were 2.68 and 8.14 µg mL−1, resp. Stress testing stability studies showed atazanavir sulfate to degrade under acidic and basic conditions. The suggested technique is simple, rapid and sustainable. It is, therefore, suggested for routine analysis of atazanavir sulfate.

For unconventional reservoirs, water flooding performs poorly because of low displacement efficiency; gas flooding shows limited enhanced oil recovery (EOR) capability due to gas breakthrough. Carbonated water injection (CWI) and active CWI (ACWI) are promising EOR methods which combine advantages of water and gas flooding. This paper provides experimental and numerical studies of carbonated water and surfactant injection based on a case study in Changqing Oilfield, China, which is the first time to investigate the feasibility of CWI and ACWI for tight oil reservoirs. This study compares performances of active water injection (AWI), CWI, Water altering gas (WAG), and ACWI. Experimental results reveal that the oil recovery of CWI is 2.7% more than WAG. ACWI achieves the highest incremental oil recovery (9.43%) among four methods. The sensitivity analyses of ACWI + WAG is further implemented experimentally, which demonstrates that ACW as a pre-flood improves 7% of oil recovery during WAG process. For Changqing tight reservoir cores, the optimal injection volume of ACW is 0.8 pore volume. Numerical simulations are conducted to validate the capability of cubic Equation-of-State coupled with Henry's law (EOS/H model) for CWI in tight oil reservoirs, indicating EOS/H model is applicable to correlate phase behavior of carbonated water and oil system. This paper, for the first time, investigates the EOR performance of ACWI in tight oil reservoirs. These results explore the feasible application of using CWI/ACWI in tight oil reservoir development.

Introdução: O p-fenilenodiamina (PPD), amina aromática sensibilizante, vem sendo adicionado ao pó de hena para modificar sua cor natural para preta, aumentando seu tempo de fixação, prática proibida em tinturas para cílios e sobrancelhas. Objetivo: O objetivo deste estudo foi otimizar e validar, em níveis intralaboratoriais, um método analítico por CLAE/UV para identificação e quantificação de PPD em tinturas de hena para cabelos e sobrancelhas. Método: Foi utilizada coluna em fase reversa C8, fase móvel trietanolamina 1% (pH 8,4) e acetonitrila (99:1, v/v), detecção a 280 nm, volume de injeção de 10 μL, fluxo 1,0 mL/min, temperatura da coluna 32°C, tempo de corrida 10 min, linearidade 5-45 μg/mL (n = 5) com coeficiente de correlação de 0,9982. Para o teste de Cochran (homocedasticidade), 0,3350 e o Ccrítico (0,3934), com 99% de confiança. Limites de detecção, 1,17 μg/mL e quantificação, 3,54 μg/mL. O coeficiente de variação da repetibilidade 0,12% e na precisão intermediária pelo teste F obteve-se p-valor de 0,283 com 95% de confiança. Resultados: Os resultados da exatidão compreenderam os critérios de aceitação (90%-107%). Das 19 amostras analisadas, 14 apresentaram teor de PPD entre 1,74% a 3,65% p/p, em desacordo com a Legislação. Conclusões: O método proposto poderá contribuir com o monitoramento da qualidade e segurança de uso destes produtos.

Cell injection plays an important role in genetics, transgenics, molecular biology, drug discovery, reproductive study, and other biomedical fields. Compared with manual cell microinjection and robotic cell microinjection with sole position feedback, force-assisted robotic cell microinjection can improve the success rate and survival rate of cell injection. In this paper, the state-of-the-art research on microinjection of both adherent cells and suspended cells with microforce sensing techniques is reviewed. The significance of force sensors in the robotic cell injection system is also discussed. Five types of prevalent force sensing methods and their applications in cell microinjection are reviewed. The challenges and promising solutions in automating the cell microinjection process are addressed. Note to Practitioners —Microinjection process is a complex task to perform. As the advance progress of high-performance microforce sensors, force-assisted robotic cell injection has been a hot topic in recent years. This paper presents the state-of-the-art survey of recent developments on microforce sensing for robotic cell microinjection to address the research challenges. Based on microforce sensing and control, microinjection of both adherent and suspended cells can benefit from the force-assisted robotic cell injection process. The main challenges and promising solutions in terms of micromanipulator design, injection control design, cell holder design, penetration scheme design, injecting pipette maintenance, injection volume, cost reduction, and microforce sensor calibration issues have been discussed. The related research trends are summarized.

The present study aimed to develop an HPLC method of Cfp analysis which enjoyed highly linearity, repeatability, robustness, ruggedness, selectivity, rapidly, and economic to use. The chromatographic method uses a column Inertsil ODS-3 (250 mm × 4.6 mm × 5 µm). The mobile phase consists of a mixture of acetonitrile: acetate buffer (4:6, v/v) at isocratic flow rate 1.5 mL/min with PDA detector at 240 nm, column oven adjusted at 30 °C, and injection volume 20 µL. The method revealed that satisfied linearity regression R2 (0.9998) with repeatability (0.77%) with LOD and LOQ: 1.102 µg/mL and 3.340 µg/mL respectively. The method showed a successful application of analytical method validation for Cfp in bulk and pharmaceutical formulations.

The objective of the method was to develop a simple, rapid, sensitive, precise, accurate and validated Ultra Performance Liquid Chromatographic (UPLC) method for the estimation of Ticagrelor in tablet dosage form. Chromatographic separation was achieved on an acquity UPLC BDS C8 (150 x 4.6 mm, 5m) column with a mobile phase composed of Buffer 0.1% OPA (2.2 pH) and Acetonitrile in the ratio of 60:40 at a flow rate of 1.0 ml/min and 1 μl injection volume. The effluents were detected at a wavelength of 240 nm using TUV detector. The retention time of Ticagrelor was found to be at 0.942 min. %RSD of the Ticagrelor was found to be 0.7 The method was validated with respect to specificity, accuracy, linearity, precision, robustness. The correlation coefficient for Ticagrelor was found to be 0.999. Recovery of Ticagrelor in formulation was found to be 99.51% . LOD, LOQ values obtained from regression equations of Ticagrelor were 0.45, 1.35 respectively. Due to simplicity, high precision and rapidness the method can be successfully applied for estimation of Ticagrelor in tablet dosage form. Keywords: Ultra Performance Liquid Chromatographic, Ticagrelor, Tablet dosage form.

This study investigates the critical parameters which influence the residual oil recovery by alkaline-surfactant-alternated-gas/CO2 (ASAG) flooding. A series of lab-scale core flood experiments were carried out with sandstone reservoir cores and Assam crude oil to examine the oil recovery potential by various schemes of ASAG flooding. The coreflood results demonstrated that ASAG flooding recovers higher residual oil (23.06% original oil in place, OOIP) compared to surfactant-alternated-gas (SAG: 18.29% OOIP) and water-alternated-gas (WAG: 8.84% OOIP) flooding processes. Effects of key parameters such as injection volume ratio, tapering, reservoir rock property, number of cycles and injection schemes on oil recovery during ASAG flooding were investigated. These factors affect the performance of ASAG flooding to an extent similar to WAG and SAG flooding.

Samryeongbaekchul-san (SBS) is a traditional herbal formula, which is used for the treatment of dyspepsia, chronic gastritis, and anorexia in Korea. To evaluate the quality of SBS decoction by quantifying its main constituents simultaneously using high-performance liquid chromatography coupled with photodiode array (HPLC–PDA) detection, and secondly to determine the antiadipogenic effect of SBS decoction. The main constituents in a 10-μL injection volume of the decoction were separated on Gemini C18 and Luna NH2 columns (both 250 mm × 4.6 mm, 5 μm) at 40 °C using a gradient of two mobile phases eluting at 1.0 mL/min. 3T3-L1 preadipocytes were differentiated into adipocytes for 8 days with or without SBS. After differentiation, accumulated triglyceride contents and leptin production were measured. The correlation coefficients of all constituents in a calibration curve were ≥0.9998 and showed good linearity in the tested concentration range after validation of the method established. The recovery of the four major compounds were 99.46–102.61% with intra- and interday precisions of 0.08–1.01% and 0.15–0.99%, respectively. The four compounds in the lyophilized SBS sample were detected up to 6.46 mg/g. SBS treatment of the differentiated adipocytes significantly inhibited lipid accumulation and leptin production without cytotoxicity. Optimized simultaneous determination of constituents by HPLC–PDA detection will help to improve quality assessment of SBS or related formulas. SBS has an antiadipogenic effect and further investigation to establish the mechanisms of action of its antiadipogenic effect is warranted. Keywords: Antiadipogenic effect, HPLC–PDA, Samryeongbaekchul-san, Simultaneous quantification, Traditional Korean medicine

A new simple, rapid and sensitive reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed by employing Quality by Design (QbD) approach for determination of levetiracetam and pyridoxine HCl in prepared tablets. Levetiracetam and pyridoxine HCl are co-administered because treatment with the antiepileptic levetiracetam leads to a deficiency in pyridoxine HCl. Fractional factorial design (FFD) was applied for screening of the four independent factors: pH of the aqueous part of the mobile phase, flow rate, injection volume and % of the organic modifier. Analysis of variance (ANOVA) confirmed that the four factors were significant. Optimization of the chromatographic conditions was performed using central composite design (CCD). The Analysis was achieved on BDS Hypersil C8 (250 × 4.6 mm, 5 μm) column applying an isocratic mobile phase containing MeOH and 25 mM KH2PO4 buffer pH 3 (38.4:61.6, v/v) at 0.8 mL/min flow rate with UV detection at 214 nm and 5 μL injection volume. The proposed method was validated according to ICH guidelines. Under optimized conditions, linear ranges of 1.56–100 μg/mL and 0.39–100 μg/mL were obtained for levetiracetam and pyridoxine HCl, respectively, with correlation coefficients (R2) of 0.999. The average recoveries ranged from 95.46 to 101.14%. The inter- and intra-day precisions were lower than 1%. The proposed method showed good predictability and robustness.