Solubility-limited absorption

Due to the small emission and absorption cross sections of Er +, a high Er density is needed to reach reasonable values of optical gain. Typically Er densities are between 0.1% and 1.0% (10 -10- Er/cm- ). These values are far beyond the equilibrium solubility limits of Er in silicon. Therefore, nonequilibrium methods have to be used, such as ion implantation. Er implantation in crystalline silicon leads to amorphization, and additional annealing (600°C) is required to... 

II Low solubility/High Peff IVIVC should be possible to establish provided that in vitro relevant dissolution test method are used and drug absorption is limited by dissolution rate rather than saturation solubility... 

The second situation when IVIVC is not likely for class II drugs is where the absorption is limited by the saturation solubility in the gastrointestinal tract rather than the dissolution rate, as discussed in more detail above. In this situation, the drug concentration in the gastrointestinal tract will be close to the saturation solubility, and changes of the dissolution rate will not affect the plasma concentrationtime profile and in vivo bioavailability. Standard in vitro dissolution tests are carried out under sink conditions , i.e., at concentrations well below the saturation solubility. Thus, only effects related to dissolution rate can be predicted in vitro. If more physiologically relevant dissolution media are used, which do not necessarily provide sink conditions , the possibility for IVIVC could be improved, as has been indicated by the results of recent studies using simulated intestinal medium [76],... 

Lipid solubility. For nonionizable compounds, as the lipophilicity increases, the drug permeability typically increases. To maximize the absorption rate, a drug should be available in the salivary film at its solubility limit. 

Intramuscular and subcutaneous administration involves absorption from the injection site into the circulation by passive diffusion. The rate of absorption is limited by the size of the capillary bed at the injection site and by the solubility of the drug in the interstitial fluid.3 If blood flow is increased at the administration site, absorption will be increased. Conversely, if blood pressure is decreased for any reason (such as cardiogenic shock) absorption will be prolonged. 

In many cases in drug development, the solubility of some leads is extremely low. Fast dissolution rate of many drug delivery systems, for example, particle size reduction, may not be translated into good Gl absorption. The oral absorption of these molecules is usually limited by solubility (VWIImann et al., 2004). In the case of solubility limited absorption, creating supersaturation in the Gl Luids for this type of insoluble drugs is very critical as supersaturation may provide great improvement of oral absorption (Tanno et al., 2004 Shanker, 2005). The techniques to create the so-called supersaturation in the Gl Luids may include microemulsions, emulsions, liposomes, complexations, polymeric micelles, and conventional micelles, which can be found in some chapters in the book. 

Many reduce bioavailability at low doses for drugs with solubility-limited absorption (drug partitioning into micelle, resulting in lower concentration of the free drug)... 

There are a number of physicochemical properties of an API that are impacted upon size reduction, which need to be considered while resolving pharmaceutical problems related to solubility limitations. Clearly, dissolution rate and its dependence upon particle size reduction is one of those critical properties (Ross and Morrison, 1988 Rabinow, 2004 Kocbek et al., 2006). For example, in the case of oral administration of a poorly water-soluble API, the increase in dissolution rate attendant with size reduction provides for more drug in solution, and available for absorption, during its gastrointestinal transit (Chaumeil, 1998 Merisko-Liversidge et al., 2003 Patravale et al., 2004 Pouton, 2006). 

The authors also studied the influence of the chain length of alkylmaltosides on the nasal absorption of enoxaparin. The results indicated that increases in the concentration of alkylmaltosides increased the AUC for plasma anti-factor Xa it was found that the absolute and relative bioavailabilities of enoxaparin increased by twofold with an increase in alkyl chain length from 8 to 14 carbons. Of all the alkylmaltosides, TDM was found to be the most potent absorption enhancer [85], Furthermore, we have also shown the efficacy of cyclodextrins in enhancing absorption following the nasal delivery of LMWHs. Three different cyclodextrins were employed P-cyclodextrins (P-CD), hydroxypropyl p-CD (FIPP-CD), and dimethyl P-CD (DM(5-CD). P-CD showed therapeutic levels of anti-factor Xa only at 2.5 and 5% p-CD, but there was no significant difference between the two concentrations, which was attributed to their solubility limit. In the case of HPP-CD, neither 1.25 nor 2.5% produced an appreciable increase in anti-factor Xa levels ... 

When one of the solvents has a limited and low solubility, C, we find the classic Langmuir absorption isotherm is obtained with a sli t modification to the activity axis as shown in Figure 9.13. Such a solubility limit can be obtained by precipitation cn- micellization in the case of surfactants. Micellization is the association of ionized surfactant molecules into structures where the hydrophobic parts of the surfactant molecules expel water. Micelles have different structures (i.e., spheres, cylinders, and lamellar structures) depending on the surfactant molecule and its concentration of surfactant in solution. Each structure has a different maximum concentration, C , which limits adsorption. In Figure 9.13, the activity is replaced by concentration in the dilute solution case and the ooncentraticm axis C2 becomes dimensionless by division by the solubility limit when the constant b is replaced by 6C in equation 9.40. 

For some drugS/ absorption is limited by a compound s solubility/ with dissolution being highly dependent on gastric pH. The antiretroviral agent didanosine/ for example/ is an acid-labile compound/ originally formulated as a buffered preparation to improve its bio availability. Other medications/ such as atazanavir and certain azole antifungals (particularly... 

A variety of methods have been used to characterize the solubility-limiting radionuclide solids and the nature of sorbed species at the solid/water interface in experimental studies. Electron microscopy and standard X-ray diffraction techniques can be used to identify some of the solids from precipitation experiments. X-ray absorption spectroscopy (XAS) can be used to obtain structural information on solids and is particularly useful for investigating noncrystalline and polymeric actinide compounds that cannot be characterized by X-ray diffraction analysis (Silva and Nitsche, 1995). X-ray absorption near edge spectroscopy (XANES) can provide information about the oxidation state and local structure of actinides in solution, solids, or at the solution/ solid interface. For example, Bertsch et al. (1994) used this technique to investigate uranium speciation in soils and sediments at uranium processing facilities. Many of the surface spectroscopic techniques have been reviewed recently by Bertsch and Hunter (2001) and Brown et al. (1999). Specihc recent applications of the spectroscopic techniques to radionuclides are described by Runde et al. (2002b). Rai and co-workers have carried out a number of experimental studies of the solubility and speciation of plutonium, neptunium, americium, and uranium that illustrate combinations of various solution and spectroscopic techniques (Rai et al, 1980, 1997, 1998 Felmy et al, 1989, 1990 Xia et al., 2001). 

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