Solubility, of drugs

It is poorly soluble in acetone, 2-butanone, ethyl acetate, acetonitrile, and DMF, and insoluble in alcohols, petroleum ether, and diethyl ether. The partition coefficients of a number of solutes between PCL and water have been measured and correlated with octanol-water partition coefficients (Fig. 9) (58,59). The linear correlation (Eq. 2) when combined with the water solubility of the solutes serves as a method of estimating the solubility of drugs in PCL from first principles. ... 

Balakin, K., Savchuk, N., Tetko, I. In silica approaches to prediction of aqueous and DM SO solubility of drug-like compounds trends, problems and solutions. Curr. Med. Chem. 2006, 13, 223-241. 

Klamt, A., Eckert, F., Homig, M., Beck, M., Burger, T. Prediction of aqueous solubility of drugs and pesticides with COSMO-RSJ. Comp. Chem. 2002, 23, 275-281. 

Q = saturation solubility of drug (macroparticles) y = interfacial tension between drug particles and the solubilizing fluids M = Molecular weight of the drug r = radius of the microscopic drug particle R = ideal gas constant... 

SD Mithani, V Bakatselou, CN TenHoor, JB Dressman. Estimation of the increase in solubility of drugs as a function of bile salt concentration. Pharm Res 13 163-167, 1996. 

To summarize, the hydration status of the drug molecule and other components of a pharmaceutical formulation can affect mass transport. Solubility of drug crystals in an aqueous or nonaqueous solvent may depend on the presence or absence of moisture associated with the drug. Hydration may also determine the hydrodynamic radii of molecules. This may affect the frictional resistance and therefore the diffusion coefficient of the drug molecules. Diffusion of drugs in polymeric systems may also be influenced by the percent hydration of the polymers. This is especially tme for hydrogel polymers. Finally, hydration of... 

Faller and Wohnsland [18, 19] developed the PAMPA assay using phospholipid-free hexadecane, supported on 10 pm-thick polycarbonate filters, and were able to demonstrate interesting predictions. Their PAMPA method appeared to be a satisfactory substitute for obtaining alkane/water partition coefficients, which are usually very difficult to measure directly, due to the poor solubility of drug molecules in alkanes. Apparently, membrane retention was not measured. 

The measurement of the solubility of drugs in polar and non-polar media is very important in the pharmaceutical field. One method proposed to describe this solubility is the partition coefficient between octanol and water. The mathematical calculation of an octanol-water partition coefficient from values for functional groups was first proposed by Hansch et al. as Hansch s n constants,1 and was later developed by Rekker as hydrophobic fragmental constants (logP).2 This method was further improved by the use of molecular connectivities.17 The prediction of logP values can be performed by either a computer program or by manual calculation. For example, approximate partition coefficients (log P) have been calculated by Rekker s method ... 

Wohnsland and Faller ([175] performed measurements using a thin (9-10 //in) supported, phospholipid-free hexadecane layer. To validate their model, they used 32 well-characterized chemically diverse compounds. The permeability values obtained with their model could be correlated with known human absorption values if the maximum permeability obtained at different pH was taken into account. However, several disadvantages are related to this method. For hydrophilic drugs, hexadecane by itself has an increased barrier function in comparison with membranes. In addition, the hexadecane layers are not very stable, which makes this assay difficult to apply as a routine screening method. The advantage of this PAMPA setup is that it appears to be a satisfactory substitute for obtaining alkane-water partition coefficients, which are usually very difficult to measure directly, due to the poor solubility of drug molecules in alkanes. 

The main input parameter used to define the highest possible drug concentration in the intestine and to calculate the dissolution rate in the GI tract is the solubility of the dmg in the GI fluids. As described earlier (Sect. 21.2) there are several, both physiological and physicochemical, factors that can affect the solubility in the GI tract and it is therefore important to consider the relevance of the solubility data generated in the early drug discovery phase. A common approach is to use in silico models to predict the solubility of drugs (e.g., [5]). The advantage of this approach is that only the chemical... 

Increase concentration of drug substance in sample solution Increased detector signal Solubility of drug substance, decreasing linearity of signal, peak broadening or instable currents due to overloading effects... 

It has been found that the solubility of drug in the polymer is influenced by the temperature of the extrusion process (30). 

Bustamante, P., S. Romero, A. Pena, B. Escalera, and A. Reillo, Enthalpy-entropy compensation for the solubility of drugs in solvent mixtures Paracetamol, acetanilide, and nalidixic acid in dioxane-water , J. Pharrn. Sci., 87, 1590-1596 (1998). 

Jouyban et al. (2004) applied ANN to calculate the solubility of drugs in water-cosolvent mixtures, using 35 experimental datasets. The networks employed were feedforward back-propagation errors with one hidden layer. The topology of neural network was optimized in a 6-5-1 architecture. All data points in each set were used to train the ANN and the solubilities were back-calculated employing the trained networks. The difference between calculated solubilities and experimental... 

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