Poorly soluble compounds

De Morsier A, J Blok, P Gerike, L Reynolds, H Wellens, WJ Bontinck (1987) Biodegradation tests for poorly-soluble compounds. Chemosphere 16 269-277. 

V. DISSOLUTION OF POORLY SOLUBLE COMPOUNDS IN SURFACTANT SOLUTIONS... 

As with micelle-facilitated dissolution, emulsion-facilitated dissolution has gained renewed interest due to its application to water-insoluble drug delivery and enhanced absorption. Over the years, emulsion systems have been developed and used to either model the in vivo dissolution process or mimic the intestinal surfactant system to enhance drug delivery of poorly soluble compounds [54-66], Emulsions have also been used as vehicles for drug delivery, e.g., to protect... 

D Oh, RL Curl, GL Amidon. Estimating the fraction dose absorbed from suspension of poorly soluble compounds in humans A mathematical model. Pharm Res 10 264-270, 1993. 

For highly permeable, poorly soluble drugs given in lower doses, the dissolution rate rather than the saturation solubility is the limiting factor. An increase in dissolution rate due to in vivo solubilization mediated by food intake could theoretically be obtained, but this situation is not always found in vivo. For example, food does not affect the rate and extent of bioavailability for candesartan cilexitil, a very poorly soluble compound [78], An in vitro dissolution and solubility study of this compound in simulated intestinal media provided a potential explanation it was revealed that the solubility was increased as a function of bile concentration as expected, whereas the dissolution rate was not increased by the higher bile concentrations being representative for the fed state (see Fig. 21.14). Thus, although... 

Environmental chemicals occur as pure liquid or solid compounds, dissolved in water or in nonaqueous liquids, volatilised in gases, dissolved in solids (absorbed) or bound to interfaces (adsorbed). Figure 5 gives a schematic view of the different physical states at which substrates are taken up by microbial cells. There is a consensus that water-dissolved chemicals are available to microbes. This is obvious for readily soluble chemicals, but there is also clear evidence for microbial uptake of the small dissolved fractions of poorly water soluble compounds. Rogoff already had shown in 1962 that bacteria take up phenanthrene from aqueous solution [55], In the intervening time many other researchers have made the same observation with various combinations of microorganisms and poorly soluble compounds [14,56,57]. 

Rohrs BR. Dissolution method development for poorly soluble compounds. Dissolution Technol 2001 8(3) 6—12. 

This case study deals with the transfer of a complex, proprietary delivery system into a CMO. The delivery system was developed to better deliver poorly soluble compounds, using Alkermes proprietary Nanocrystal Colloidal Dispersion (NCD ) system. The major challenges associated with the transfer of this technology into an Alkermes production facility (Anon, 2012), included ... 

Some in vitro ADME and safety assays (e.g., microsomal stability and hERG blockade) may not be possible with poorly soluble compounds. 

The division of the intermediates of the reaction pathway into three groups is characteristic CoA compounds, diphosphates, and highly lipophilic, poorly soluble compounds (squalene to cholesterol), which are bound to sterol carriers in the cell. 

Formidable chemical obstacles stood in the way of clinical development of these agents derived from natural products, notably in formulation of very poorly soluble compounds for intravenous infusion and in manufacture of bulk drug. For a time, production of Taxol from the bark of the Pacific Yew tree aroused public controversy, which became a story of nature and politics in pursuit of an anti-cancer drug [22]. 

The applicability of PBPK models can be described in the context of the BDDCS classification [24]. PBPK models are very predictive for class 1 and class 2 compounds. However for poorly soluble compounds, the use of aqueous solubility is shown to be inadequate for reliable prediction of oral absorption in physiologically based models [7]. In such cases, it is recommended to use solubility measured in simulated intestinal fluids (FeSSIF, FaSSIF). Such data proved to be very relevant to simulate the oral absorption of BCS 2 (low solubility, high permeability) compounds [25]. 

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