Poorly water-soluble compound

Poorly water-soluble compounds were previously discussed as to the cause of poor water solubility - the large lipophilic greaseballs and the brickdust compounds [15] which are poorly water soluble because of strong intermolecular crystal... 

DMSO is much less of a good solvent for the poorly water-soluble brickdust compound because the breaking of a strong inter-molecular crystal lattice is pretty well unchanged whether the solvent is water or DMSO. The breaking of the strong crystal lattice is the primary cause of poor water solubility for the pure brickdust compound. The further a poorly water-soluble compound is into the brickdust camp, the less effective is DMSO as a solvent. 

Repeating for emphasis - not aU poorly water-soluble compounds are equally solubilized by DMSO. The greaseball compounds will be much better solubilized than the brickdust compounds. The most common range of compound in DMSO stock concentrations in compound storage repositories is 2-20 mM. At conferences, organizations employing 2mM compound in DMSO stock solutions report fewer solubility problems. The downside is that the lower stock concentrations are more Hmited in utility in some absorption, distribution, metabolism, excretion and toxicity assays that require higher compound concentration. 

WR Perkins, I Ahmad, X Li, DJ Hirsh, GR Masters, CJ Fecko, JK Lee, S Ali, J Nguyen, J Schupsky, C Herbert, AS Janoff, E Mayhew. Novel therapeutic nano-particles (lipocores) trapping poorly water soluble compounds. Int J Pharm 200(l) 27-39, 2000. 

Saha, P. and J. Kou. Effect of solubilizing excipients on permeation of poorly water-soluble compounds across Caco-2 cell monolayers., Eur. 

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]. 

E. Merisko-Liversidge, G.G. Liversidge and E.R. Cooper, Nanosizing a formnlation approach for poorly-water-soluble compounds, Eur. J. Pharm. Sci., 18, 113-120 (2003). 

Taken together, these results indicate that dehydrated cells could be an alternative catalyst for the conversion of poorly water-soluble compounds and that it might be possible to treat a mixture of pollutants by combining strains. Nevertheless, for future application the improvement of catalyst stability is still needed and is currently being studied. 

Kwon GS. Polymeric micelles for delivery of poorly water-soluble compounds. Crit Rev Ther Drug Carrier Syst 2003 20(5) 357-403. 

For example, this effect was seen with the complex formed between alfaxalone, a poor water-soluble compound, and HP-p-CD (Peeters et al., 2002). 

For formulating poor water-soluble compounds, use of cosolvent(s) is one of the simplest and common approach. The approach is also widely used in the early development phase, as limited information is available for the molecule. The approach also allows overcoming dissolution rate limited drug absorption. In addition, solubilized formulations are greatly popular with pediatric, geriatric, and patients with swallowing difculties. 

Table 17.2 illustrates the absolute oral bioavailability of several Danazol formulations nanoparticle dispersion, solubilized cyclodextrin oral formulation, and conventional suspension. Danazol represents a poorly water-soluble compound (H /mL) whose oral bioavailability is dissolution limited. 

There have been a number of formulation approaches explored and widely practiced in the pharmaceutical industry to improve delivery of poorly water-soluble compounds especially in development of immediate release dosage forms. These delivery approaches are based on various techniques described as following ... 

Delivery systems that use a multicompartment core can theoretically deliver drugs of any solubility [48,49], A basic Push-Pull System consists of two layers the Lrst contains the drug, osmotically active hydrophilic polymer(s), and other pharmaceutical excipients the second layer, often called the push layer, contains a hydrophilic expansion polymer, other osmotically active agents, and the excipients, as shown in Figure 22.6. Poorly water-soluble compounds can be delivered using an ORO Push-Pull tlelivery system by incorporating drug as a micronized form, or as a hot-melt material suspended in a polymer matrix. 

Following oral administration, dissolution of the drug molecule in the intestinal milieu is a prerequisite for the absorption process. According to the Biopharmaceutical Classification System (BCS) [2], poor water-soluble compounds (i.e., aqueous solubility less than 100 pg/ mL) are class 2 or class 4 compounds. For class 2 compounds, the absorption level is dictated by the dissolution properties of the molecule in the gastrointestinal (GI) fluids. BCS class 4 compounds, which are characterized by both low solubility and poor intestinal wall permeability, are generally poor drug candidates (unless the dose is very low). 

Chan, O.H., et al. 1998. Evaluation of a targeted prodrug strategy to enhance oral absorption of poorly water-soluble compounds. Pharm Res 15 1012. 

Polymeric micelles formed by Pluronics, PEG phospholipid conjugates, PEG-b-polyesters, or PEG-b-poly-L-amino acids were proposed for drug delivery of poorly water-soluble compounds, such as amphotericin B, propofol, paclitaxel, and photosensitizers [77,86,87]. It was also emphasized that using polymeric micelles can significantly increase the drug transport into the brain. 

Currently, most mature dissolution controlled release systems/ technologies are applicable for water-soluble and low-water-solubility compounds (with low doses). For very poorly water-soluble compounds, dissolution controlled release systems/technologies may not be applicable because these compounds have intrinsically slow dissolution/release rates. Recently, several new technologies such as solid dispersions and self-emulsifying drug delivery systems (SEDDS) have been developed to deliver poorly water-soluble compounds at reasonable doses through enhancement of dissolution rate. These technologies have created new potentials for controlled release of poorly water-soluble compounds, often... 

K. Shiraki, N. Takata, R. Takano, Y. Hayashi, K. Terada, Dissolution improvement and the mechanism of the improvement from cocrystallization of poorly water-soluble compounds, Pharm. Res. 25 (2008) 2581-2592. 

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