Solubility bioavailability

The reactivity and transformation to yield soluble bioavailable species of metalbearing substances are expected to be significantly affected by the high chloride content and other unique chemical characteristics of marine waters. 

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. 

In summary, it appears that although the atmospheric iron input to the global ocean is dominated by dry deposition ( 70%), the input of soluble, bioavailable iron comes largely through wet deposition. Jickells and Spokes [82] combine these observations to estimate an overall solubility of atmospheric iron in seawater of 0.8-2.1% of the total Fe deposition flux, resulting in a soluble, bioavailable iron flux to the oceans of 13-67 x 10 °gyear . This accounts for a large fraction of the iron input at many locations in the ocean [117-121]. 

To meet these metabolic requirements, nature has developed protein ligands which maintain iron in a soluble, bioavailable form while preventing it from catalyzing reactions that produce harmful oxidative products. These iron-binding proteins are transferrin, lactoferrin, and ferritin. 

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. 

Polymorphism is a characteristic of the solid state and the concept is immensely important in the pharmaceutical industry. Properties such as stability, solubility, bioavailability, manufacturability, tableting, formulation, and even toxicity are a function of the polymorph crystal structure. 

A major reason for the popularity of pharmaceutical co-crystals in industry is that they lend themselves well to patent protection. They admirably satisfy the three criteria of patentability, namely novelty, non-obviousness and utility. A co-crystal almost always satisfies the novelty criterion because it is a new composition of matter. Non-obviousness is provided by the fact that the identification of the co-former is hardly ever routine, unlike say salt formation wherein an acid is obviously required to make a salt from a base. Utility is generally the only criterion that must be established but it is often easy to demonstrate—usually it is the lack of a particular attribute (solubility, bioavailability, dissolution profile, good shelf life) that has led to the identification of a pharmaceutical co-crystal. With respect to patentability, co-erystals offer opportunities vis-d-vis polymorphs. They are clearly new substances, problems of inherent anticipation are not likely to arise so often and more of them can be made for any given API, expanding the pharmaceutical space around it and consequently the types of advantageous properties that may be accessed. 

---