Solvent Injection Research Articles

Acid resilience oral mucosal delivery for vaccination against Hepatitis-B

The predominant mode of transmission for the viral infection that causes hepatitis B as the major reason of liver cirrhosis and hepatocellular carcinoma is by the parenteral or permucosal route. M-cell targeted acid-resistant oral vaccine administration has been developed for Hepatitis B infection prevention. The solvent injection approach was used to create cationic solid lipid nanoparticles (cSLNs). Alginate-coated cSLNs loaded with hepatitis B surface antigen (HBsAg) were conjugated with lipopolysaccharide (LPS). To assess the produced formulation's resistance against acid degradation, SDS-PAGE was used. ELISA assays were used to measure anti-HBsAgIgG/IgA antibodies in mucosal fluids after female Balb/c mice were used to determine the induction of immunity induced by manufactured nanoparticle for hepatitis B infection prevention. After 48 h, alginate-coated cSLNs showed sustained releasing of HBsAg compared to cSLNs devoid of alginate coating. Anti-HBsAG was produced in the intestinal, salivary, and vaginal secretions at levels that were comparatively elevated in comparison to that of the control group, which had an anti-HBsAG titer of 0.25 IU/ml. After binding with SLN, the M-cells' integrity was preserved, and the oral administration helped the antigen reach the gut where it was most needed. It was discovered to be successful at generating antibodies during the mucosal immunization against the hepatitis B virus. As a result, LPS-conjugated alginate-coated cSLNs loaded with HBsAg offers a promising substitute for an existing vaccine for the prevention of hepatitis B infection.

Box-Behnken Design for Formulation, Characterization and In-vivo Antidiabetic Activity of Pioglitazone Loaded Nanostructured Lipid Carriers

This study employs a 23 full factorial design in the design of experiment (DOE) technique to assess the impact of critical quality attributes (CQAs) on critical process parameters (CPPs) in the formulation of pioglitazone (PGZ) loaded nanostructured lipid carriers (NLCs). The three chosen CPPs are the quantity of liquid lipid (Captex 300), the proportion of solid lipid (Glyceryl Palmitostearate), and the amount of surfactant. The CQAs evaluated are entrapment efficiency (%EE) and particle size. The PGZ-loaded NLCs are prepared through a solvent injection method. The lipid phase, consisting of dissolved medication and lipids in ethanol, is rapidly injected into an aqueous phase containing the surfactant. The resulting dispersion undergoes analysis for entrapment effectiveness and particle size. Additionally, the in-vivo antidiabetic activity of the optimal formulation is examined using diabetic rat models induced by streptozotocin (STZ), and relevant biochemical parameters are assessed. The results demonstrate that the proposed PGZ-loaded NLCs exhibit superior antidiabetic activity and favorable physicochemical characteristics compared to free PGZ. This study provides valuable insights into the formulation and characterization of NLCs for enhanced diabetes management, emphasizing their potential as a promising delivery system to improve the therapeutic efficacy of antidiabetic drugs like PGZ

Formulation of shea butter-based lipid nanoparticles for topical and transdermal applications

Introduction: Shea butter is a natural lipid widely used in topical formulations because of its hydrating, anti-inflammatory and regenerative properties on the skin. The aims of this study was to develop lipid- based nanoparticles using local shea butter as building material for topical and transdermal applications. Methods: The nanoparticles of shea butter were made using three different processes (high shear homogenization, phase inversion temperature or solvent injection techniques. The formulation factors were optimized. The obtained nanoparticle suspensions were evaluated for particle size using dynamic light scattering, polydispersity index, zeta potential and physicochemical stability. Subsequently the aqueous colloidal suspension obtained by high shear homogenization technique was converted into a gel by adding 0,5 % Carbopol 980NF (polymer) as a gelling agent and subsequent neutralization with sodium hydroxide. The gel formulations were investigated for pH and viscosity measurements at day
 
 The viscosity was assessed at 26°C using a rotational viscometer STS-2011 (shear rate of 2 s-1, spindle n°R4, 10 rpm).
 
 Results: The optimized conditions make it possible to obtain nanoparticles with average sizes of 54.1 ±
 5.0 nm, 99.1 ± 1.0 nm and 161.5 ± 4.4 nm, when the phase inversion temperature, high shear homogenization or the solvent injection techniques were respectively used. All optimized formulations
 
 showed a narrow size distribution and the zeta potential values were between -20 and -38 mV depending on the technique used. The three colloidal suspensions were considered physically stable at room temperature for at least three months as no significant changes in mean size, polydispersity index or zeta potential values were observed. The gel formulations exhibited viscosities of 32 800 ±100 mPa.s with pH values of 5,0 ± 0,5.
 Conclusion: In order to evaluate their potential as a new carrier system for skin delivery and as a follow- up to these promising initial results, morphological analysis of the nanosystems and evaluation of their encapsulation capacity are in progress, before in vitro skin permeation and retention studies are considered.

Dual Rifampicin and Isoniazid Mannose-Decorated Lipopolysaccharide Nanospheres for Macrophage- Targeted Lung Delivery.

Currently, the treatment protocols for tuberculosis (TB) have several challenges, such as inconsistent oral bioavailability, dose-related adverse effects, and off-target drug toxicity. This research reports the design and characterization of rifampicin (RIF) and isoniazid (INH) loaded hybrid lipid-polysaccharide nanoparticles using the solvent injection method, and demonstrated the influence of conjugated mannosyl residue on macrophage targeting and intracellular drug delivery capacity. The nanospheres, herein called mannose-decorated lipopolysaccharide nanoparticles, were spherical in shape, exhibiting average sizes less than 120 nm (PDI<0.20) and positive zeta potentials. Drug encapsulation was greater than 50% for rifampicin and 60% for isoniazid. The pH-responsive drug release was sustained over a 48-hour period and preferentially released more rifampicin/isoniazid in a simulated acidic phagolysosomal environment (pH 4.8) than in a simulated physiological medium. TGA and FTIR analysis confirmed successful mannose-grafting on nanoparticle surface and optimal degree of mannosylation was achieved within 48-hour mannose-lipopolysaccharide reaction time. The mannosylated nanoparticles were biocompatible and demonstrated a significant improvement towards uptake by RAW 264.7 cells, producing higher intracellular RIF/INH accumulation when compared to the unmannosylated nanocarriers. Overall, the experimental results suggested that mannose-decorated lipopolysaccharide nanosystems hold promise towards safe and efficacious macrophage-targeted delivery of anti-TB therapeutics.

Polysorbate 80 surface modified SLNs of formoterol suppress SNCA gene and mitochondrial oxidative stress in mice model of Parkinson’s disease

The present study hypothesises that the selective brain β2 receptor activation through β2-adrenoreceptor agonist (β2ARA), Formoterol (FMT), suppresses SNCA gene expression, a pathological hallmark of Parkinson’s disease (PD) in brain. Further, it is also hypothesized that brain targeted delivery of Formoterol via polysorbate-80 surface modified solid lipid nanoparticles of Formoterol (FMT-SLNs-PS80) can improve its stability, therapeutic efficacy and avoid/reduce peripheral off-target side effects. FMT-SLNs-PS80 was prepared by solvent injection method, the formulation was optimized by using Box–Behnken design and characterized by measuring drug content, entrapment efficacy, particle size, zeta potentials and poly dispersibility. The FMT-SLNs-PS80, significantly decreases the SNCA expression, mitochondrial membrane damage and rotenone induced changes in oxidative (SOD, CAT, GSH and ROS) stress markers in SH-SY5Y cell lines. The ex vivo permeation study of the formulation using everted chicken ileum exhibited a steady state flux. The pharmacokinetic and tissue distribution studies of the formulation in rats showed a significant improvement in the kinetic parameters when compared to naïve FMT, further the formulation also improved the brain bioavailability of FMT. The anti-Parkinson’s efficacy studies of the formulation in mice showed a significant neuroprotection against rotenone-induced changes in behavioural and biochemical parameters. Further, the histopathological analysis of mice brain confirms a significant neuroprotective benefit. The present study successfully establishes the brain targeted delivery and anti-Parkinson’s therapeutic efficacy of FMT-SLNs-PS80.

Improved sample introduction approach in hydrophilic interaction liquid chromatography to avoid breakthrough of proteins

When therapeutic proteins are analysed under hydrophilic interaction liquid chromatography (HILIC) conditions, there is an inherent mismatch between the sample diluent (proteins must be solubilised in aqueous media) and the mobile phase, which is mostly composed of aprotic solvent (acetonitrile). This difference in eluent strength between sample diluent and mobile phase is responsible for severe analyte breakthrough and peak distortion. As demonstrated with therapeutic proteins of different sizes (insulin of 6 kDa, anakinra of 17 kDa and rituximab subunits of 25 and 50 kDa), only very small volumes of 0.1–0.2 µL can be injected without breakthrough effects, when performing rapid analysis on short HILIC columns of 20–50 mm, leading to poor sensitivity. In order to avoid the undesired effect of the strong sample diluent, a special injection program should be preferred. This consists in the addition and automatic injection of a defined volume of weak solvent (acetonitrile) along with the sample to increase retention factors during sample loading. Various injection programs were tested, including the addition of a pre-injection or post-injection or both (bracketed injection) of acetonitrile plugs. Several weak to strong injection solvent ratios of 1:1, 1:2, 1:4 and 1:10 were tested. Our work proves that the addition of a pre-plug solvent with a weak vs. strong injection solvent ratio of 1:10 is a valuable strategy to inject relatively large volumes of proteins in HILIC, regardless of column dimensions, thus maximising sensitivity. No peak deformation or breakthrough was observed under these conditions. However, it is important to note that peak broadening (40 % larger peaks) was observed when the injection program increased the injection solvent ratio from 1:1 to 1:10. Finally, this strategy was applied to a wide range of therapeutic mAb products with different physico-chemical properties. In all cases, relatively large volumes can be successfully injected onto small volume HILIC columns using a purely aqueous sample diluent, as long as an appropriate (weak) solvent pre-injection is applied.

Apolipoprotein E3 functionalized lipid-drug conjugated nanoparticles of Levetiracetam for enhanced delivery to the brain: In-vitro cell line studies and in-vivo study

A significant portion of brain-tumor patients suffer from ‘brain-tumor-related epilepsy (BTE)’ which results in depression, anxiety and hampered quality of life. Conventional anti-epileptic drugs indicate negative interaction with other drugs augmenting the poor outcome of overall therapy. Levetiracetam (LVM) has evidenced effectiveness for BTE but its hydrophilicity restricts the passage into blood-brain barrier. The majority of lipid nanoparticles fails to load hydrophilic drug sufficiently. Therefore, lipid-drug conjugates (LDC) were synthesized using stearic acid via amide bond formation confirmed by FTIR and NMR. The nanoparticles of synthesized LDC were prepared by solvent injection method followed by functionalization with Apolipoprotein E3 (ApoE3@LDC-NP). The nanoparticles were characterized by DSC, XRD, particle size (131.6 ± 1.24 nm), zeta potential (−15.6 ± 0.09 mV), and for storage stability. In-vitro release study indicated initial burst release of 20 ± 0.63 % followed by sustained release up to 30 h (66 ± 1.40 %) for ApoE3@LDC-NP. The cell-line study on HEK293 indicated no significant cytotoxic effect and greater cell uptake through U87MG cell line. The pharmacokinetic and bio-distribution study indicated 2.5-fold greater brain-targeting of ApoE3@LDC-NP as compared to LVM solution. It proved safe in the haemolysis study and exhibited the absence of tissue necrosis. Thus, ApoE3@LDC-NP might be a promising approach for effective brain-targeting of LVM for improved clinical response in BTE.

Multiphase Multicomponent Transport Modeling of Cyclic Solvent Injection in Shale Reservoirs

Summary A thorough understanding of fluid transport in ultratight shale reservoirs is crucial for designing and optimizing cyclic solvent injection processes, known as huff ’n’ puff (HnP). We develop a two-phase multicomponent numerical model to investigate hydrocarbon and solvent transport and species mixing during HnP. Unlike the conventional modeling approaches that rely on bulk fluid (advective) transport frameworks, the proposed model considers species transport within nanopores. The chemical potential gradient is considered the driving force for the movement of nonideal fluid mixtures. A binary friction concept is adopted that considers friction between different fluid molecules and between fluid molecules and pore walls. After validating the developed model against analytical solutions and experimental data, the model examines solvent HnP enhanced oil recovery (EOR) mechanisms by considering four-component oil and Eagle Ford crude oil systems. The impacts of injection pressure, primary production duration, soaking time, and solvent type on the oil recovery are examined. The results reveal that the formation of a solvent-oil mixing zone during the huff period and oil swelling and vaporization of oil components during the puff period are key mechanisms for enhancing oil recovery. Furthermore, the incremental recovery factor (RF) increases with injection pressure, even when the injection pressure exceeds the minimum miscibility pressure (MMP), implying that MMP may not play a critical role in the design of HnP in ultratight reservoirs. The results suggest that injecting solvents after a sufficient primary production period is more effective, allowing reservoir pressure depletion. Injecting the solvent without enough primary production may result in significant production of the injected solvent. The results show that the solvent-oil mixing zone expands, and the solvent recycling ratio decreases as soaking time increases. However, short soaking periods with higher HnP cycles are recommended for improving oil recovery at a given time frame. Finally, CO2 HnP outperforms CH4 or N2 HnP due to the higher ability of CO2 to extract a larger amount of intermediate and heavy components into the vapor phase, which has higher transmissibilities as compared with the liquid phase.

Development of LC-MS/MS analytical method for the rapid determination of Diquat in water and beverages

This study aimed to develop simple, fast, and sensitive methods for the determination of diquat (DQ) in various matrices such as water and beverages. For water, direct injection was tested first, however, the sensitivity of the incurred samples were too low and couldn’t possibly achieve the targeted limit of quantification. Hence, dilution with “weaker” injection solvents were tested, and the final conditions involved the dilution of water with acetonitrile (0.4 % ammonium hydroxide) which increased the sensitivity by more than ten times. Nevertheless, the beverages samples needed further treatment to achieve acceptable spiked recovery. The final conditions involved extraction using the aforementioned solvent, followed by heating and partitioning. Both of the methods satisfied the validation requirements, with an average recovery ranging from 85.9 to115 % and associated relative standard deviation (RSD %) within the range 3–8. Further applications on real samples were done to test the levels of contamination.

One‐Pot/Simultaneous Synthesis of PHPMA‐G‐PLA Copolymers via Metal‐Free Rop/Raft Polymerization and their Self‐Assembly from Micelles to Thermoresponsive Vesicles

AbstractThe present article reports a simple and straightforward approach to access thermoresponsive graft copolymers based on lactide (LA) and a methacrylic monomer, 2‐hydroxypropyl methacrylate (HPMA), using a synthesized carboxy‐functionalized trithiocarbonate‐based chain transfer agent. One protocol involves a metal‐free simultaneous synthesis through a combination of reversible addition‐fragmentation chain transfer polymerization and organic acid‐catalyzed ring‐opening polymerization, which follows first‐order kinetics. The resulting copolymers with a controlled structure exhibit remarkably narrow molecular weight distributions (Ð &lt; 1.10). Within this framework, the self‐assembly of PHPMA‐g‐PLA graft copolymers (GCs) into nanoparticles (NPs) is demonstrated at concentrations of 0.2 and 0.5 wt.%, respectively. The displacement method, based on the rapid injection of the organic solvent (acetone) into an aqueous medium under vigorous stirring, produces spherical NPs such as micelles, vesicles, or non‐spherical “lumpy rods”. The presence of a pseudo‐thermoresponsive segment (PHPMA) in GCs facilitates stimulus‐responsive self‐assembly behavior. Well‐defined spherical NPs—primarily vesicles of substantial size—develop upon heating above the glass transition temperature (Tg ≈35–36 °C) of the GCs in an acetone–water (80/20 wt.%) mixture. Last, specific interactions between the obtained PHPMA‐g‐PLA nano‐objects and blood proteins in human plasma are studied using isothermal calorimetry.

The power of sulfhydryl groups: Thiolated lipid-based nanoparticles enhance cellular uptake of nucleic acids

AimThe aim of the study was to evaluate the effect of thiolation of lipid-based nanoparticles (LNPs) on cellular uptake of nucleic acids. MethodsA thiolated surfactant was synthesized by binding palmitic acid covalently to cysteine. Green fluorescent protein (GFP) encoding plasmid DNA (pDNA) was used as model nucleic acid and incorporated via hydrophobic ion-pairing with a cationic cholesterol derivate (DcCholesterol) in LNPs that were prepared by solvent injection method using the thiolated surfactant for surface decoration. LNPs were characterized regarding size, polydispersity index, zeta potential and stability in biorelevant media. The endosomal escape properties of LNPs were evaluated by erythrocytes interaction studies. Cell viability and transfection efficiency on HEK293 cells were investigated. ResultsThe structure of the thiolated surfactant was confirmed by 1H NMR and FT-IR. LNPs containing the nucleic acid-DcCholesterol complex with and without the thiolated surfactant were developed and displayed sizes in the range from 173 nm to 233 nm with a narrow size distribution (PDI < 0.3) and a negative zeta potential. LNPs showed no significant increase in size after 4 h of incubation in artificial body fluids. Erythrocytes interaction studies revealed enhanced endosomal escape properties for thiolated LNPs compared to non-thiolated LNPs. LNPs showed in concentrations lower than 0.74 mg/mL cell viability ≥ 80 %. Transfection studies on HEK cells with thiolated LNPs compared to non-thiolated LNP showed a 4.6-fold higher expression of GFP. ConclusionSurface thiolation of LNPs represents a promising tool for enhancing intracellular nucleic acid delivery of LNPs.

Rapid screening, isolation, and activity evaluation of potential xanthine oxidase inhibitors in Polyporus umbellatus and mechanism of action in the treatment of gout.

Studies show that Polyporus umbellatus has some pharmacological effects in enhancing immunity and against gout. We aimed to establish new techniques for extraction, biological activity screening, and preparation of xanthine oxidase inhibitors (XODIs) from P.umbellatus. First, the extraction of P.umbellatus was investigated using the back propagation (BP) neural network genetic algorithm mathematical regression model, and the extraction variables were optimised to maximise P.umbellatus yield. Second, XODIs were rapidly screened using ultrafiltration, and the change of XOD activity was tested by enzymatic reaction kinetics experiment to reflect the inhibitory effect of active compounds on XOD. Meanwhile, the potential anti-gout effects of the obtained active substances were verified using molecular docking, molecular dynamics simulations, and network pharmacology analysis. Finally, with activity screening as guide, a high-speed countercurrent chromatography (HSCCC) method combined with consecutive injection and two-phase solvent system preparation using the UNIFAC mathematical model was successfully developed for separation and purification of XODIs, and the XODIs were identified using MS and NMR. The results verified that polyporusterone A, polyporusterone B, ergosta-4,6,8(14),22-tetraen-3-one, and ergosta-7,22-dien-3-one of P.umbellatus exhibited high biological affinity towards XOD. Their structures have been further identified by NMR, indicating that the method is effective and applicable for rapid screening and identification of XODIs. This study provides new ideas for the search for natural XODIs active ingredients, and the study provide valuable support for the further development of functional foods with potential therapeutic benefits.

Polyphosphate coated nanoparticles: Enzyme-activated charge-reversal gene delivery systems

AimThe current study aimed to develop enzyme-activated charge-reversal lipid nanoparticles (LNPs) as novel gene delivery systems. MethodsPalmitic acid was covalently bound to protamine being utilised as transfection promoter to anchor it on the surfaces of LNPs. Green fluorescent protein (GFP) encoding plasmid DNA (pDNA) was ion paired with various cationic counter ions to achieve high encapsulation in LNPs. Protamine-decorated LNPs were prepared by solvent injection method followed by coating with sodium tripolyphosphate (TPP) to generate a bio-inert anionic outer surface. Resulting LNPs were characterised regarding size, polydispersity, zeta potential and encapsulation efficiency. Enzyme-triggered charge-reversal of LNPs was investigated using isolated alkaline phosphatase (ALP) monitoring changes in zeta potential as well as monophosphate release. Furthermore, monophosphate release, cell viability and transfection efficiency were evaluated on a human alveolar epithelial (A549) cell line. ResultsProtamine-decorated and TPP-coated (Prot-pDNA/DcChol-TPP) LNPs displayed a mean size of 298.8 ± 17.4 nm and a zeta potential of −13.70 ± 0.61 mV. High pDNA encapsulation was achieved with hydrophobic ion pairs of pDNA with 3ß-[N-(N',N'-dimethylaminoethane)-carbamoyl]cholesterol hydrochloride (DcChol). Zeta potential of Prot-pDNA/DcChol-TPP LNPs reversed to positive values with a total Δ26.8 mV shift upon incubation with ALP. Conformably, a notable amount of monophosphate was released upon incubation of Prot-pDNA/DcChol-TPP LNPs with isolated as well as cell-associated ALP. A549 cells well tolerated LNPs displaying more than 95 % viability. Compared with naked pDNA, unmodified LNPs and control LNPs, Prot-pDNA/DcChol-TPP LNPs showed a significantly increased transfection efficiency. ConclusionProt-pDNA/DcChol-TPP LNPs can be regarded as promising gene delivery systems.

Activation of CYP3A by ABC phenomenon potentiates the hepatocellular carcinoma-targeting therapeutic effects of PEGylated anticancer prodrug liposomes.

Reduced enzyme activity in hepatocellular carcinoma (HCC) and poor targeting limit the application of enzyme-activating prodrugs, which is also detrimental to the effective treatment of HCC. Here, we investigated whether accelerated blood clearance (ABC) phenomenon occurs in HCC models following repeated injections of PEGylated liposomes (PEG-L), thus inducing prodrugs accumulation and activation in the liver and exerting highly effective and low-toxicity therapeutic effects on HCC. Firstly, PEGylated liposomal cyclophosphamide (PEG-CP-L) was prepared by solvent injection and characterized. Importantly, pre-injection of PEG-L induced ABC phenomenon and activation of CYP3A in both HCC rats and HCC mice by investigating the effects of repeated injections of PEG-L on pharmacokinetics and tissue distribution. Next, the efficacy and toxicity of repeated injections of PEG-L in HCC mice were examined, and our data indicate that repeated injections are administered in a manner that significantly enhances the antitumor effect compared to controls with little or no toxicity to other organs. To further reveal the pharmacokinetic mechanism of PEG-L repeated administration for the treatment of HCC, the protein expression of hepatic CYP3A and the concentration of CP in the liver and spleen of HCC mice by inhibiting CYP3A were analyzed. These results revealed that inducing CYP3A to accelerate the rapid conversion of prodrugs that accumulate significantly in the liver is a key mechanism for the treatment of HCC with repeated injections of PEG-L. Collectively, this work taps into the application potential of the ABC phenomenon and provides new insights into the clinical application of PEGylated nanoformulations. Significance Statement This study revealed that repeated injections of PEG-L could induce the ABC phenomenon characterized by hepatic accumulation and CYP3A activation based on HCC rats and HCC mice. Furthermore, it was verified that induction of the ABC phenomenon dependent on hepatic accumulation and CYP3A activation could enhance the anti-hepatocellular carcinoma effects of PEGylated anticancer prodrugs in HCC mice. This elucidated the relevant pharmacokinetic mechanisms and unearths new clues for solving the clinical application of PEGylated nanoparticles.

Long term suppression of deep traps in CsPbBr3 nanocrystals by introducing slight lattice distortion

CsPbX3 (X = Br, Cl, I) nanocrystals have broad application prospects, due to their high luminescent efficiency and low preparation cost. However, the stability of CsPbBr3 nanocrystals prepared using conventional methods is poor; thus, large-scale applications have not yet been achieved. Currently, most of the methods aimed at improving the stability of CsPbBr3 nanocrystals involve inorganic or organic encapsulation, which makes it challenging to apply them to devices that operate with electrical injection. In this article, we report that CsPbBr3 nanocrystals prepared by the solvent quenching method, without any external encapsulation, can maintain excellent optical properties after long-term storage. Through the studies of temperature-dependent photoluminescence spectroscopy, X-ray photoelectron spectroscopy, and Raman spectroscopy, we have revealed that the nanocrystals prepared by solvent injection quenching method contain slight lattice distortion of the [PbBr]64- cages, which can lead to the formation of shallow trap states while suppressin the formation of deep traps, thereby maintaining excellent optical properties for long time.

Experimental evaluation of the impact of induced fractures on cyclic solvent injection performance in low-permeability hydrocarbon reservoirs

Recovery factors associated with primary recovery (pressure depletion) schemes are often small (<5–10%) for low-permeability hydrocarbon reservoirs. As a result, cyclic solvent injection (CSI) schemes, using CO2 and produced gas, are currently being considered for enhanced hydrocarbon recovery (EOR). Fracture networks, generated during hydraulic fracturing stimulation, affect both primary and enhanced recovery by increasing the surface area contacted with the low-permeability reservoir matrix. However, experimental studies of the impact of induced (hydraulic) fractures on CSI performance are sparse, particularly those that provide a realistic representation of the fracturing process by inducing fractures under stress to better represent fracture conditions (e.g., fracture surface area, fracture surface roughness). Therefore, the primary objective of this work is to develop a laboratory-based workflow for evaluating the effectiveness of fracture system in tight oil reservoirs to enhance the oil recovery during a typical CSI cycle using a combination of core-scale techniques.An in-house core-flooding methodology, that combines ‘in situ’ fracturing and cyclic gas injection, was applied. The experimental procedure includes: 1) performing multiple cycles of lean gas (i.e., 80% C1 + 20% C2) injection into an oil-saturated ‘intact’ core plug until maximum oil recovery (5%) is reached, 2) artificially fracturing the core plug under stress, 3) repeating multiple cycles of lean gas injection into the artificially-fractured core plug, under similar experimental conditions as those used for the intact core, until maximum oil recovery (23%) is reached, and 4) measuring the fractured-core liquid permeability. A well-characterized tight siltstone core plug sample obtained from the Canadian Montney Formation was analyzed as an example. The experimental results indicate that 1) fracturing under stress results in an increase in surface area and permeability, and 2) the recovery factor is enhanced by ∼ 18% after fracturing (e.g., from ∼ 5% for intact core plug to ∼ 23% for artificially-fractured core plug).This study provides a proof-of-concept experimental approach for evaluating the impact of induced fractures on CSI recovery using an identical core plug sample (intact and fractured). The proposed experimental methodology could serve as a workflow for laboratory-scale evaluation of the impact of induced fractures on CSI performance in tight hydrocarbon reservoirs.

Influence of solvent injection temperature in steam-solvent assisted gravity drainage process for heavy oil reservoirs of Brazilian Northeast

The solvent–steam assisted gravity drainage is an oil recovery process that combines the advantages of thermal and miscible effects, and it has been successfully tested, especially in Canada, where many heavy oil reservoirs are located. This method uses two parallel horizontal wells drilled one above the other, the upper injects steam and solvent and the lower produces oil. This process has not been applied yet in Brazil, where there are heavy oil reservoirs, especially in northeast region. Based on this context, this research aimed to study the application of the ES-SAGD process in a semisynthetic reservoir, with characteristics similar to those found in the Brazilian Northeast, specifically to analyze the influence of the solvent injection scheme on ES-SAGD. Numerical simulations were performed using commercial software from CMG. It was analyzed several steam-solvent injection rates, using two injected temperatures for solvent, (at reservoir or at steam temperature´s), in order to minimize explosion risks, that can be due to high temperatures. Results showed that solvent injection temperature has great influence on oil recovery, it is better for oil production when it is inject hot solvent, because cold solvent generates a cooling of the steam. However, it is possible to injected cold solvent (at reservoir temperature), and increase oil production, changing some steam properties, avoiding explosions risks.

Propane–Bitumen Interactions during Cyclic Solvent Injection─A Cold Lake Case Study

Propane–Bitumen Interactions during Cyclic Solvent Injection─A Cold Lake Case Study

Comparative Static and Dynamic Analyses of Solvents for Removal of Asphaltene and Wax Deposits above- and below-Surface at an Iranian Carbonate Oil Field.

During production from oil wells, the deposition of asphaltene and wax at surface facilities and porous media is one of the major operational challenges. The crude oil production rate is significantly reduced due to asphaltene deposition inside the reservoir. In addition, the deposition of these solids inside the surface facilities is costly to oil companies. In this study, the efficiency of different solvents in dissolving asphaltene and wax was investigated through static and dynamic tests. The analysis of solid deposits from the surface choke of one of the Iranian carbonate oil fields showed that they consisted of 41.3 wt % asphaltene, and the balance was predominantly wax. In addition, the asphaltenes obtained from the surface choke solid deposits had a more complex structure than that of asphaltenes extracted from the crude oil itself. The static tests showed that xylene, toluene, gasoline, kerosene, and gas condensate had the highest efficiencies in dissolving solid deposits; conversely, diesel had a negative impact on dissolving solid deposits. Static tests on pure asphaltene showed that, among the tested solvents, gas condensate and diesel had a negative effect on the solubility of asphaltene. The dynamic core flooding results showed that asphaltene deposition inside the cores reduced the permeability by 79-91%. Among the tested solvents, xylene, gasoline, and kerosene resulted in the highest efficacy in restoring the damaged permeability, and higher efficiency was obtained with an equivalent solvent injection rate of 1 bbl/min versus 3 bbl/min.

A laboratory investigation of CO2 influence on solvent-assisted polymer flooding for improving viscous oil recovery on Alaska North Slope

In this study, the CO2 influence on enhancing Alaska North Slope (ANS) viscous oil recovery for polymer flooding with assistance of solvents is investigated. Seven coreflooding tests were conducted at reservoir conditions to evaluate ANS viscous oil recovery performance of five solvent-assisted EOR methods including LHS (light hydrocarbon solvent)-alternating-LSW (low salinity water) flooding, CO2-enriched LHS-alternating-LSW flooding, LHS-alternating-LSP (low salinity polymer) flooding, CO2-enriched LHS-alternating-LSP flooding, and CO2-enriched LHS-LSW-LSP flooding. Besides, the CO2 influence on the performance of solvent-assisted EOR methods is investigated. In addition, Constant Composition Expansion (CCE) tests were performed at reservoir temperatue of 85 °F to explore mechanisms of oil recovery improvement with solvent injection in EOR methods of this study. Moreover, water ion analyses of DI-water/natural-sand and DI-water/natural-sand/CO2 systems were carried out to discover the complex reaction between CO2, sand, and LSP solution for better understanding underlying mechanisms of solvent-assisted EOR methods. Coreflooding experiment results demonstrate that five proposed EOR methods all present remarkable production performance with recovery factor ranging from 79.73% to 92.23%. The main EOR mechanisms can be attributed to oil swelling and viscosity reduction effects resulting in the enhancement of microscopic displacement efficiency during solvent flooding and the improvement of macroscopic sweep efficiency of subsequent LSW/LSP flooding resulting from obtaining better mobility control. Considering the recovery factor from the 1st solvent flooding, no obvious improvement was observed with solvent containing CO2. However, higher oil recovery improvement was obtained from the subsequent LSW/LSP flooding of tests using solvent with CO2 than that without CO2, mainly resulting from better mobility control due to the greater viscosity reduction effect by CO2-enriched LHS. Nevertheless, a severe blockage occurred at the production end in the CO2-enriched LHS-alternating-LSP flooding test, which was likely due to the polymer precipitation. CCE test results present that more solvent could be dissolved into the ANS viscous oil by increasing the pressure of the system, which causes greater oil swelling and viscosity reduction effects. The saturation pressure was affected little by adding CO2 in LHS, while the presence of CO2 had a negative impact on oil swelling effect but a positive influence on oil viscosity reduction effect. In addition, water ion analyses results show that, after introducing CO2 to the DI-water/natural-sand system, a great amount of multivalent cations were generated probably due to the dissolution of minerals in the natural sand, which may explain the polymer precipitation. Therefore, the blockage issue at the production end could be solved by injecting LSW as a spacer between CO2-enriched LHS flooding and LSP flooding to reduce the concentration of generated cations.