Petroleum Reservoir Simulation

Drugs with low water solubility are predisposed to low and variable oral bioavailability and, therefore, to variability in clinical response. Despite significant efforts to "design in" acceptable developability properties (including aqueous solubility) during lead optimization, approximately 40% of currently marketed compounds and most current drug development candidates remain poorly water-soluble. The fact that so many drug candidates of this type are advanced into development and clinical assessment is testament to an increasingly sophisticated understanding of the approaches that can be taken to promote apparent solubility in the gastrointestinal tract and to support drug exposure after oral administration. Here we provide a detailed commentary on the major challenges to the progression of a poorly water-soluble lead or development candidate and review the approaches and strategies that can be taken to facilitate compound progression. In particular, we address the fundamental principles that underpin the use of strategies, including pH adjustment and salt-form selection, polymorphs, cocrystals, cosolvents, surfactants, cyclodextrins, particle size reduction, amorphous solid dispersions, and lipid-based formulations. In each case, the theoretical basis for utility is described along with a detailed review of recent advances in the field. The article provides an integrated and contemporary discussion of current approaches to solubility and dissolution enhancement but has been deliberately structured as a series of stand-alone sections to allow also directed access to a specific technology (e.g., solid dispersions, lipid-based formulations, or salt forms) where required.

Strategies to Address Low Drug Solubility in Discovery and Development

In this paper, theoretical and experimental approaches to flow, hydrodynamic dispersion, and miscible and immiscible displacement processes in reservoir rocks are reviewed and discussed. Both macroscopically homogeneous and heterogeneous rocks are considered. The latter are characterized by large-scale spatial variations and correlations in their effective properties and include rocks that may be characterized by several distinct degrees of porosity, a well-known example of which is a fractured rock with two degrees of porosity---those of the pores and of the fractures. First, the diagenetic processes that give rise to the present reservoir rocks are discussed and a few geometrical models of such processes are described. Then, measurement and characterization of important properties, such as pore-size distribution, pore-space topology, and pore surface roughness, and morphological properties of fracture networks are discussed. It is shown that fractal and percolation concepts play important roles in the characterization of rocks, from the smallest length scale at the pore level to the largest length scales at the fracture and fault scales. Next, various structural models of homogeneous and heterogeneous rock are discussed, and theoretical and computer simulation approaches to flow, dispersion, and displacement in such systems are reviewed. Two different modeling approaches to these phenomena are compared. The first approach is based on the classical equations of transport supplemented with constitutive equations describing the transport and other important coefficients and parameters. These are called the continuum models. The second approach is based on network models of pore space and fractured rocks; it models the phenomena at the smallest scale, a pore or fracture, and then employs large-scale simulation and modern concepts of the statistical physics of disordered systems, such as scaling and universality, to obtain the macroscopic properties of the system. The fundamental roles of the interconnectivity of the rock and its wetting properties in dispersion and two-phase flows, and those of microscopic and macroscopic heterogeneities in miscible displacements are emphasized. Two important conceptual advances for modeling fractured rocks and studying flow phenomena in porous media are also discussed. The first, based on cellular automata, can in principle be used for computing macroscopic properties of flow phenomena in any porous medium, regardless of the complexity of its structure. The second, simulated annealing, borrowed from optimization processes and the statistical mechanics of spin glasses, is used for finding the optimum structure of a fractured reservoir that honors a limited amount of experimental data.

Flow phenomena in rocks : from continuum models to fractals, percolation, cellular automata, and simulated annealing

Shale gas and non-aqueous fracturing fluids: Opportunities and challenges for supercritical CO2

Hydraulic fracturing has been used by the oil and gas industry as a way to boost hydrocarbon production since 1947. Recent advances in fracturing technologies, such as multistage fracturing in horizontal wells, are responsible for the latest hydrocarbon produc- tion boom in the US. Linear or crosslinked guars are the most commonly used fluids in traditional fracturing operations. The main functions of these fluids are to open/propagate the fractures and transport proppants into the fractures. Proppants are usually applied to form a thin layer between fracture faces to prop the fractures open at the end of the fracturing process. Chemical breakers are used to break the polymers at the end of the fracturing process so as to provide highly conductive fractures. Concerns over fracture conduc- tivity damage by viscous fluids in ultra-tight formations found in unconventional reservoirs prompted the industry to develop an alter- native fracturing fluid called "slickwater". It consists mainly of water with a very low concentration of linear polymer. The low concentration polymer serves primarily to reduce the friction loss along the flow lines. Proppant-carrying capability of this type of fluids is still a subject of debate among industry experts. Constraints on local water availability and the potential for damage to formations have led the industry to develop other types of fracturing fluids such as viscoelastic surfactants and energized fluids. This article reviews both the traditional viscous fluids used in conventional hydraulic fracturing operations as well as the new family of fluids being devel- oped for both traditional and unconventional reservoirs. V C 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131 ,4 0735.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/app.40735

A review of fracturing fluid systems used for hydraulic fracturing of oil and gas wells

A Method for Determining the Optimum Location of Wells in a Reservoir Using Mixed-Integer Programming

Water-based polymer gels are used widely in the oil and gas industry to viscosify fluids used in the hydraulic fracturing of production wells, where they serve to increase the force applied to the rock and to improve the transport of proppants used to maintain the fracture after formation. After fracturing, the gel must be degraded to a low viscosity with enzymes or gel breakers. Existing systems add the breaker either directly to the gelant or encapsulated in beads that are crushed when the applied pressure is released and the fractures close. In the former case, the gel may be broken prematurely, and this may prevent efficient fracture propagation and proppant trans- port, whereas in the latter case, the breaker may not be uniformly distributed throughout the gel, with the result that the gel is incompletely broken and the hydraulic con- ductivity of the well is reduced. To obtain delayed release, combined with the homogeneous distribution of enzyme throughout the gel, polyethylenimine-dextran sulfate poly- electrolyte complexes were used to entrap pectinase. Such particles were originally developed to entrap pharmaceuti- cals, and we previously demonstrated their ability to delay the release of gel crosslinking agents for oilfield applica- tions. The degradation of both the viscosity and visco- elastic moduli of borate-crosslinked guar gel by pectinase loaded in polyelectrolyte nanoparticles was delayed by up to 12 h, compared to about 2 h for equivalent systems where the pectinase was not entrapped. The combination of homogeneous mixing and the delayed release of enzymes packaged in polyelectrolyte complex nanopar- ticles showed promise for improved cleanup after hydra- ulic fracturing. V C 2011 Wiley Periodicals, Inc. J Appl Polym Sci 121: 1292-1298, 2011

/pdf/fracturing-fluid-cleanup-by-controlled-release-of-enzymes-23k2yix4cn.pdf

Don W. Green

Papers

A Method for Determining the Optimum Location of Wells in a Reservoir Using Mixed-Integer Programming

Fracturing fluid cleanup by controlled release of enzymes from polyelectrolyte complex nanoparticles

Experimental Study of the Gelation Behavior of a Polyacrylamide/Aluminum Citrate Colloidal-Dispersion Gel System

Formation and Propagation of Gel Aggregates Using Partially Hydrolyzed Polyacrylamide and Aluminum Citrate

The Effect of Fluid Leakoff on Gel Placement and Gel Stability in Fractures