Purpose: To develop a system of liquids that can mimic the x‐ray properties of breast tissue having varying percentages of glandular tissue. These liquids are being used to provide a variable tissue ...composition for a cylindrical phantom designed for experimental studies of x‐ray spectra for breast CT. Methods: A mathematical algorithm for designing tissue substitutes has been described in the literature. The method requires knowledge of the elemental composition of the tissue being simulated. Information for breast tissue can be obtained from the paper by Hammerstein et al., or from ICRU Report 46. The method also requires the use of three materials to form the substitute. The three materials chosen for this application are isopropyl alcohol, glycerin, and water. These materials are inexpensive, readily available, miscible, and relatively non‐toxic. Many other choices are possible. Results: The calculated linear attenuation coefficients of the mixtures match the calculated coefficients of the tissue being simulated with errors of a fraction of a percent over the energy range 10 to 100 keV. The measured linear attenuation coefficients of the mixtures match the calculated coefficients of the tissues being simulated to an accuracy of 5%. Conclusion: A system of common, readily available liquids that can accurately match the narrow‐beam attenuation properties of breast tissue with glandular percentages from 100% to 22.5 % has been described. Computational results were confirmed by experiment.
Aqueous solubility is a key physicochemical attribute required for the characterisation of an active pharmaceutical ingredient (API) during drug discovery and beyond. Furthermore, aqueous solubility ...is highly important for formulation selection and subsequent development processes. This review provides a summary of simple predictive methods used to assess aqueous solubility as well as an assessment of the more complex in silico methodologies and a review of the recent solubility challenge. In addition, a summary of experimental methods to determine solubility is included, with a discussion of some potential pitfalls.
The solubility of four lignin samples and their acetylated forms was determined in a series of organic solvents to investigate the relationship between solubility and the solubility parameter. The ...solubility parameter of lignin samples and acetylated lignin was calculated based on the number of atoms or groups on lignin units. Lignin samples were obtained by isolating lignin from lignocellulosic bioethanol residues (Lignin 1 L1), isolating lignin from kraft hardwood black liquor (Lignin 2 L2), commercial kraft softwood lignin (Lignin 3 L3), and commercial soda non-wood lignin (Lignin 4 4). The solubility of lignin in organic solvents was not predictable due to poor correlation between the solubility of lignin and its solubility parameter. However, the solubility of lignin in an organic solvent depended on the molecular weight and the aliphatic hydroxyl number of the lignin. L2, with a lower molecular weight than other lignin samples, had the highest solubility in organic solvents, and L3, with highest aliphatic hydroxyl number, had the lowest solubility in organic solvents. All acetylated lignins were soluble in most of the organic solvents. Furthermore, the molecular weights of the soluble parts of all four lignins in ethyl acetate were found to be lower than the original lignins.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Poor aqueous solubility is a major challenge in today's biopharmaceutics. While solubility-enabling formulations can significantly increase the apparent solubility of the drug, the concomitant effect ...on the drug's apparent permeability has been largely overlooked. The mathematical equation to describe the membrane permeability of a drug comprises the membrane/aqueous partition coefficient, which in turn is dependent on the drug's apparent solubility in the GI milieu, suggesting that the solubility and the permeability are closely related, exhibit a certain interplay between them, and treating the one irrespectively of the other may be insufficient. In this article, an overview of this solubility–permeability interplay is provided, and the available data is analyzed in the context of the effort to maximize the overall drug exposure.
Overall, depending on the type of solubility–permeability interplay, the permeability may decrease, remain unchanged, and even increase, in a way that may critically affect the formulation capability to improve the overall absorption. Therefore, an intelligent design of solubility-enabling formulation needs to consider both the solubility afforded by the formulation and the permeability in the new luminal environment resulting from the formulation.
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Current solvents used in membrane preparation are often toxic, environmentally unfriendly and prepared from non-sustainable resources. It would be beneficial to replace common solvents, like
N
,
N
...-dimethylacetamide (DMA),
N
,
N
-dimethylformamide (DMF) and tetrahydrofuran, by "green" solvents. Among these, bio-based solvents were selected for this research, more specifically γ-valerolactone (GVL) and a set of glycerol derivatives. They were screened for their potential use as solvent for membrane preparation by determining solubility of a variety of common membrane polymers and by verifying their applicability in the process of phase inversion to create useful membranes with appropriate pore structures and separation properties. Polymer solubility was rationalized by Hansen solubility parameters. Membrane morphology was characterized by using scanning electron microscopy, while membrane performance was investigated using rose bengal (1017 Da) in water as feed to screen the potential to tune these polymer/solvent systems even toward the nanofiltration range.
Current solvents used in membrane preparation are often toxic, environmentally unfriendly and prepared from non-sustainable resources.
While each of the two key parameters of oral drug absorption, the solubility and the permeability, has been comprehensively studied separately, the relationship and interplay between the two have ...been largely ignored. For instance, when formulating a low-solubility drug using various solubilization techniques: what are we doing to the apparent permeability when we increase the solubility? Permeability is equal to the drug’s diffusion coefficient through the membrane times the membrane/aqueous partition coefficient divided by the membrane thickness. The direct correlation between the intestinal permeability and the membrane/aqueous partitioning, which in turn is dependent on the drug’s apparent solubility in the GI milieu, suggests that the solubility and the permeability are closely associated, exhibiting a certain interplay between them, and the current view of treating the one irrespectively of the other may not be sufficient. In this paper, we describe the research that has been done thus far, and present new data, to shed light on this solubility–permeability interplay. It has been shown that decreased apparent permeability accompanies the solubility increase when using different solubilization methods. Overall, the weight of the evidence indicates that the solubility–permeability interplay cannot be ignored when using solubility-enabling formulations; looking solely at the solubility enhancement that the formulation enables may be misleading with regards to predicting the resulting absorption, and hence, the solubility–permeability interplay must be taken into account to strike the optimal solubility–permeability balance, in order to maximize the overall absorption.
The solubility of oxygen in 21 pure organic solvents was measured at 298.2 K and 101.33 kPa using the static method. The Hansen solubility parameters (HSPs) of oxygen were determined from the ...measured solubilities in the pure solvents. The HSPs of oxygen were δd = 6.7 MPa1/2, δp = 0.0 MPa1/2, and δh = 3.8 MPa1/2, where d, p, and h stand for dispersion forces, dipole interaction, and hydrogen bonding, respectively. A linear relationship between the log of the gas solubility (log x G) in pure solvents and the difference between the HSP values of oxygen and the pure solvents was obtained with a high correlation coefficient of 0.944. In addition, the solubilities of oxygen in mixed solvents were measured, and these were compared with the oxygen gas solubility calculated from the HSPs of oxygen.
Experimental and computational approaches to estimate solubility and permeability in discovery and development settings are described. In the discovery setting ‘the rule of 5’ predicts that poor ...absorption or permeation is more likely when there are more than 5 H-bond donors, 10 H-bond acceptors, the molecular weight (MWT) is greater than 500 and the calculated Log P (CLogP) is greater than 5 (or MlogP>4.15). Computational methodology for the rule-based Moriguchi Log P (MLogP) calculation is described. Turbidimetric solubility measurement is described and applied to known drugs. High throughput screening (HTS) leads tend to have higher MWT and Log P and lower turbidimetric solubility than leads in the pre-HTS era. In the development setting, solubility calculations focus on exact value prediction and are difficult because of polymorphism. Recent work on linear free energy relationships and Log P approaches are critically reviewed. Useful predictions are possible in closely related analog series when coupled with experimental thermodynamic solubility measurements.
The purpose of this study was to conduct a head-to-head comparison of different solubility-enabling formulations, and their consequent solubility-permeability interplay. The low-solubility anticancer ...drug etoposide was formulated in several strengths of four solubility-enabling formulations: hydroxypropyl-β-cyclodextrin, the cosolvent polyethylene glycol 400 (PEG-400), the surfactant sodium lauryl sulfate, and an amorphous solid dispersion formulation. The ability of these formulations to increase the solubility of etoposide was investigated, followed by permeability studies using the parallel artificial membrane permeability assay (PAMPA) and examination of the consequent solubility-permeability interplay. All formulations significantly increased etoposide's apparent solubility. The cyclodextrin-, surfactant-, and cosolvent-based formulations resulted in a concomitant decreased permeability that could be modeled directly from the proportional increase in the apparent solubility. On the contrary, etoposide permeability remained constant when using the ASD formulation, irrespective of the increased apparent solubility provided by the formulation. In conclusion, supersaturation resulting from the amorphous form overcomes the solubility-permeability tradeoff associated with other formulation techniques. Accounting for the solubility-permeability interplay may allow to develop better solubility-enabling formulations, thereby maximizing the overall absorption of lipophilic orally administered drugs.
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