Percolation Characteristics and Injection Limit of Surfactant Huff-n-Puff in a Tight Reservoir.

For the development of tight reservoirs, large-scale volume fracturing is frequently utilized as an effective production enhancement strategy. However, there is a significant decrease in productivity after fracturing. Improvement of production through secondary surfactant huff-n-puff has become one of the methods. In this paper, the characteristics of surfactant percolation during huff-n-puff were analyzed from macroscopic and microscopic perspectives. The production variation characteristics of the huff-n-puff were calculated by experiments and numerical methods. From Stokes' equations and phase field equations, solutions were found to analyze the effect of interfacial properties on surfactant percolation from the microscopic perspective. The findings demonstrated that a surfactant with a high displacement efficiency could not considerably increase huff-n-puff production, whereas the percolation rate had a wider influence. The surfactant with ultralow interfacial tension (<1 × 10-2 mN/m) and a higher wetting angle (>12.6°) has a faster percolation rate. Significant huff-n-puff production can be obtained in the percolation rate range of 1.38 to 1.63 m/PV. Simultaneously, the concepts of limit and optimal injection volume were established and utilized to characterize the influence of injection parameters on production under nonextension fracture situations. Based on the data, in order to obtain high production in a short time, the injection strength should be near to the value at fracture extension, and the optimum injection volume is 1000-1200 m3/m. The findings of this study have the potential to guide the selection of the surfactant and injection parameters in the field.

Influencing Factors of Surfactant Stripping Crude Oil and Spontaneous Imbibition Mechanism of Surfactants in a Tight Reservoir.

Surfactants play a vital role in the working fluid during the exploitation of tight reservoirs. The main goal is to clarify the mechanism of surfactant production enhancement in the reservoir. In this paper, starting from the interface properties and emulsifying properties of surfactants, the factors affecting the stripping of crude oil by different surfactants were described in detail. Meanwhile, the imbibition experiments of cores were used to clarify the two spontaneous imbibition mechanisms of the surfactant. Namely, they are the capillary force expulsion caused by the emulsion stripping thermal diffusion-convection and the wettability change. When the interfacial tension between the surfactant and oil is in the range of 10-2-10-3 mN/m, the particle size of emulsion is less than 1 µm, and the oil stripping efficiency is greater than 58%. The imbibition is mainly caused by thermal diffusion-convection. The wetting angle of the surfactant mainly changing wettability is less than 15°, and the adhesion work is greater than 52 mN/m. Using X-ray computed tomography, the surfactant imbibition distance of different permeability types of cores was obtained. The results show that higher permeability cores have a deeper imbibition distance. The results of this paper enrich the mechanism of enhanced oil recovery by surfactants and have important implications for the exploitation of tight reservoirs.

A rapid 2AB-UHPLC method based on magnetic beads extraction for N-glycan analysis of recombinant monoclonal antibody.

N-glycosylation is one of the major post-translational modifications, with significant effects on the mechanism of action, the efficacy, and the safety of antibody drugs or glycoproteins. With the growing application of therapeutic antibodies, routinely monitoring N-glycosylation becomes increasingly important during cell culture process development and quality control. However, the current pretreatment methods for N-glycan analysis are time- and labor-consuming. The purification procedure of enzymatically released glycans could also partly affect the accuracy of results due to its complexity. In this study, a rapid ultra-high performance liquid chromatography method based on magnetic bead extraction and 2-AB fluorescent labeling was developed and compared against three popular pretreatment methods for N-glycan profiling (two were solid phase extraction and the other was acetone precipitation). The method's repeatability results showed that magnetic bead extraction has higher precision (% relative standard deviation (RSD), 0.121.06%) than solid phase extraction (SPE) (%RSD, 0.38-8.02%) and acetone precipitation (%RSD, 0.42-8.58%). This robust pretreatment method also maximized the retention of some low abundance oligosaccharides, and may thus provide a rapid and high-throughput workflow option for N-Glycan analysis in the biopharmaceutical industry.

Effect of different sample treatment methods on Low Endotoxin Recovery Phenomenon.

Endotoxin is a kind of lipopolysaccharide that exits on the cell wall of Gram-negative bacteria. It can cause fever, shock or even death when is delivered into human body. So, it is necessary to control the endotoxin contamination for biopharmaceutical products that are mainly administered by intravenous route. Limulus Amebocyte Lysate (LAL)-based tests are usually used to detect endotoxin content in biologics formulations. However, an undesirable phenomenon called "Low Endotoxin Recovery (LER)" often occurs in formulation buffers that usually contain chelating component, such as sodium citrate, and amphiphilic surfactant, such as Tween-20. The occurrence of this LER phenomenon may interfere with endotoxin detection and cause false negative results. In this study, we compared the effect of different sample treatment methods on endotoxin detection and found that the LER phenomenon was better controlled under the conditions of low pH (pH = 5.0), low temperature (2-8 °C) and in the presence of divalent cations in the solution. In addition, although the endotoxin activity was found to have decreased due to LER phenomenon, the particle size distribution of endotoxin determined by dynamic light scattering (DLS) in LER solution did not change obviously, which is different from previous hypothesis about LER phenomenon in literature that the particle size of endotoxin aggregates would decrease under LER conditions. These findings provide some insights into different sample treatment methods for endotoxin detection and give a better understanding and solution on minimizing the LER phenomenon.

Goserelin Acetate Loaded Poloxamer Hydrogel in PLGA Microspheres: Core-Shell Di-Depot Intramuscular Sustained Release Delivery System.

This study aimed to prepare and optimize goserelin acetate (GOS) loaded hydrogel poly(d,l-lactic acid-co-glycolic acid) (PLGA) microsphere that is suitable for long-acting clinical treatment, investigate its structure, and regulate the initial release manner. Here, the PLGA microsphere containing Poloxamer hydrogel loaded with ∼15% (w/w) GOS was prepared by double-emulsion-solvent evaporation method and evaluated in terms of microscopic structure, physicochemical properties, and release manner in vitro and in vivo. Raman volume imaging and scanning electron microscopy studies revealed a core-shell Di-Depot structure of the microsphere, in which multi-GOS-loaded hydrogel depots were distributed in the core region. Under the interaction of hydrogel and PLGA depots, high encapsulation efficiency (94.16%) and low burst release (less than 2%) were achieved, along with the accompanying prolonged administration interval (49 days); an enhanced relative bioavailability 9.36-fold higher than that of Zoladex implant was also observed. Also, by addition of 1-5% acetic acid, the lag time was shortened to 6 days. The strategy for regulating the initial release provides new insights for manipulating the release behavior of the PLGA microspheres. The desirable property of the Poloxamer hydrogel PLGA microsphere indicated its promising application in controlled release drug delivery system.

Co-delivery of latanoprost and timolol from micelles-laden contact lenses for the treatment of glaucoma.

Glaucoma is a group of irreversible ocular diseases which result in damage to the optic nerve and vision loss. The objective of the present work was to develop micelles-laden contact lenses (CLs-M) that could achieve the sustained release of timolol and latanoprost simultaneously for the treatment of glaucoma. CLs-M were obtained by free radical polymerization of HEMA monomer with timolol and latanoprost loaded mPEG-PLA micelles. The prepared CLs-M had a minimal impact on critical CLs properties, and could release timolol and latanoprost in simulated tear fluid for 144 h and 120 h individually, which is promising for extended drugs release applications. The in vivo PK study on rabbit eyes showed sustained timolol and latanoprost release for up to 120 h and 96 h in tear fluid, respectively. There was significant improvement of the mean residence time (79.6-fold and 122.2-fold) and bioavailability (2.2-fold and 7.3-fold) for both timolol and latanoprost delivered by CLs-M compared with eye drops. An in vivo PD study in a rabbit model with high IOP showed sustained reduction in the IOP for over 168 h. The relative pharmacological availability (PA) of CLs-M was 9.8 times as high as the eye drops. The protein adsorption, ocular irritation study and histological examination study indicated the safety of CLs-M. Therefore, this work has demonstrated the promising potential of micelles-laden CLs to co-deliver timolol and latanoprost for an extended period of time to treat glaucoma.