Solubility bioavailability and

The inclusion into the hydrophobic cavity causes modifications of solubility, bioavailability, and delivery properties of many bioactive molecules. Furthermore the stability of many guest molecules is improved, e.g., against... 

To increase the usefulness of bioremediation as an effective field remedial tool, significant investments have been made towards the development of means to remove sorbed PAHs, attack sources of NAPL, and subsequently increase the aqueous solubility/bioavailability, and thus the biodegradability, of targeted compounds. To date, one of the most effective ways to accomplish these tasks involves the use of surface active agents (i.e., surfactants). A variety of synthetic surfactants have been shown effective in increasing the bioavailability of PAHs and other hydrophobic contaminants (Kile Chiou, 1989, 1990 Edwards et al., 1991 Liu et al., 1991). Although the solubilization process is not completely understood, these studies showed that a variety of ionic and nonionic surfactants could significantly increase the water solubility of monitored chemicals. 

In a recent review, Shan and Zaworotko have discussed cocrystals having pharmaceutical interest, and presented several case studies that they used to demonstrate how one could enhance the solubility, bioavailability, and/or stability of drug substances [23]. The systems considered were the cocrystals of fluoxetine hydrochloride with carboxylic acids, itraconazole with dicarboxylic acids, sidenafil with acetylsalicylic acid, and melamine with cyanuric acid. One main conclusion advanced by the authors was that the use of cocrystal systems in pharmaceutical dosage forms was inevitable, and that the main questions were who would benefit and how drastic the influence on development would ultimately turn out to be. 

Polycyclic Amines Several polycyclic arylamines have carcinogenic potential. It is, however, important to note that (even slight) molecular modifications can influence solubility, bioavailability, and metabolism, and the mutagenic and carcinogenic potential of molecules. 

The most common crystalline forms are polymorphs, hydrates, and solvates (pseudopolymorphs). Polymorphs are formed when a substance crystallizes in two or more crystal structures. Polymorphism significantly impacts on physicochemical properties of materials, such as stability, density, melting point, solubility, bioavailability, and so on. Hence the characterization of all possible polymorphs, identifying the stable (thermodynamic) polymorph, and design of reliable processes for consistent production are critical in modem day drug development. 

The nasal tissue is highly vascularized and provides efficient systemic absorption. Compared with oral or subcutaneous administration, nasal administration enhances bioavailability and improves safety and efficacy. Chitosan enhances the absorption of proteins and peptide drugs across nasal and intestinal epithelia. Gogev et al. demonstrated that the soluble formulation of glycol chitosan has potential usefulness as an intranasal adjuvant for recombinant viral vector vaccines in cattle [276]. 

Drug delivery problems associated with pilocarpine, most notably low ocular bioavailability and short duration of action, continue to be significant (44). In an effort to prolong delivery and to avoid undesirable effects, an investigation was carried out on the incorporation and in vitro release of pilocarpine from a soluble film... 

The ionizability of compounds affects other parameters such as solubility, permeability, and ultimately oral bioavailability, so it may be important to track changes in the pka of new compounds. Calculated pka values can be used when planning the synthesis of new compounds, but it is also a good idea to confirm these values experimentally. An example where this strategy can be useful is in the search for bioisosteric replacements for a carboxylic acid group. 

The bioavailability of trace elements in soil-water-plant ecosystems of arid zones is largely determined by their partitioning between solution and solid-phase components. The redistribution and transformation of trace elements among solid-phase components under various biogeochemical conditions strongly adjust their lability and bioavailability. Soluble, exchangeable and organically bound forms are bioavailable to plants. The carbonate bound fraction represents a reservoir of potentially bio-available trace elements to plants. In paddy soils, the amorphous Fe/Al oxide fraction contributes to trace element availability as well. 

In the course of evolution, the importance of particular metal ions in biological systems has ebbed and flowed, as a function of environmental conditions. Before the arrival of photosynthesis, when there was no oxygen, elements like Fe and Ni were extremely important, whereas, for example, Cu was virtually inaccessible for reasons of solubility. With the arrival of an oxidizing environment, Ni virtually disappeared from the equation, Cu became bioavailable, and Fe, although it was now insoluble and poorly available, had proved of such fundamental importance in biological catalysis that specific systems were developed for its uptake from the environment, such that it continues to play a key role in life as we know it today. 

BCS Class II Low-solubility, high-permeability drugs. The bioavailability of products containing these compounds is likely to be dissolution-rate limited. For this reason, a correlation between in vivo bioavailability and in vitro dissolution rate (IVIVC) may be observed. 

This volume gives an overview of the current status and an outlook to future more reliable predictive approaches. It is subdivided in five sections dealing with studies of membrane permeability and oral absorption, drug dissolution and solubility, the role of transporters and metabolism in oral absorption, computational approaches to drug absorption and bioavailability, and finally with certain drug development issues. 

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