The definition of poor solubility

E. If protocol development is rate A. The definition of poor VII. ACCEPTABLE SOLUBILITY... 

Cleanliness of the fuel must be monitored if the fuel is naturally dirty or can pick up contaminants during transportation. The nature of the contaminants depends on the particular fuel. The definition of cleanliness here concerns particulates that can be strained out and is not concerned with soluble contaminants. These contaminants can cause damage or fouling in the fuel system and result in poor combustion. 

Lipids are a very diverse group of biochemicals that, by definition, are poorly soluble in water and are soluble in organic solvents such as ether. An important structural feature of lipids that allows these solubility characteristics is a relatively high ratio within the molecule of hydrocarbon atoms to more polar kinds of atoms. This definition allows the inclusion of tons of molecules into the lipid family, even gasoline. We will focus on the ones normily found in the body. 

In most cases, poor solubility is associated with poor oral bioavailability, because these drugs also possess a very slow dissolution velocity. An alternative administration via the intravenous route is also not possible because of the volume required for dissolution of these drugs would be too large. Therefore, with the increasing number of poorly soluble drugs, there was a definite need to overcome low oral bioavailability and the lack of i.v. injectability by a smart pharmaceutical formulation principle. 

A classic pharmaceutical science textbook might have defined poor solubility as anything below a solubility of 1 g mL-1 (2 mol L-1 solution for a molecular weight of 500 Da) at pH 6.5 (or pH 7). This classic view is reflected in the Chemical Abstracts SciFinder 2001 solubility range definitions for solubility calculated using Advanced Chemistry Development (ACD) Software Solaris V4.67. These semi-quantitative ranges for molar solubility are very soluble, 1 mol L 1 < solubility soluble, 0.1 mol L 1 < solubility < 1 mol L 1 slightly soluble, 0.01 mol L 1 <... 

The above conceptual and operational pH definitions for solutions in non-aqueous and mixed solvents are very similar to those for aqueous solutions [16]. At present, pH values are available for the RVS and some primary standards in the mixtures between water and eight organic solvents (see 5 in Section 6.2) [17]. If a reliable pH standard is available for the solvent under study, the pH can be determined with a pH meter and a glass electrode, just as in aqueous solutions. However, in order to apply the IUPAC method to the solutions in neat organic solvents or water-poor mixed solvents, there are still some problems to be solved. One of them is that it is difficult to get the RVS in such solvents, because (i) the solubility of KHPh is not enough and (ii) the buffer action of KHPh is too low in solutions of an aprotic nature [18].8) Another problem is that the response of the glass electrode is often very slow in non-aqueous solvents,9 although this has been considerably improved by the use of pH-ISFETs [19]. Practical pH measurements in non-aqueous solutions and their applications are discussed in Chapter 6. 

The decrease in Aj is attributed to two factors (1) poor solubility of solvent, since THF is not a good solvent for ionic groups (2) attraction between ion pairs in low dielectric constant medium. If the former is the only cause, we should obtain the same molecular weight irrespective of the ion content. However, as is shown in Figure 7, the molecular weight increases with ion content. Therefore, the decrease in definitely reflects the attractions between ion pairs in THF. The second virial coefficient of ionomer solutions is composed of two parts f32.331 i.e., — Ai +... 

Many discovery leads are transferred to the preclinical development process with insufficient characterization to assess their development potential. This lack of knowledge usually results in poorly designed experiments that are not data productive and that, in many cases, have to be repeated when the drug candidate shows unexpected toxicity, low and variable delivery, instability or solubility problems, or unacceptable pharmacokinetic and drug metabolism profiles. In all too many cases, the recognition of these problem areas results in termination of development for a potentially useful therapeutic agent. At best, the problems encountered cause a delay, at times substantial, in the development of a candidate while additional studies are conducted to elucidate the causes of the problems and minimize their effects. Then the definitive development experiments have to be repeated. 

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