Cosolvent method

If the compound is virtually insoluble (solubility lpgmb ), then a potentiometric mixed solvent approach can be tried [2, 28-30]. For example, the pka of the antiarrhythmic amiodarone, 9.06 0.14, was estimated from water-methanol 

The most explored solvent systems are based on water-alcohol mixtures, acetonitrile-water and DMSO-water [8], Where possible, methanol is the solvent of choice, because its general effect on pKjS has been studied so extensively. It is thought to be the least error-prone of the common solvents [28]. 

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Furthermore, pH electrode calibration can be performed in situ by the new method [48], concurrently with the pKj determination. This is a substantial improvement in comparison to the traditional procedure of first doing a blank titration to determine the four Avdeef-Bucher parameters [24]. The traditional cosolvent methods used with sparingly soluble molecules can be considerably limited in the pH<4 region when DMSO-water solutions are used. This is no longer a serious problem, and routine blank titrations are now rarely needed in the new in situ procedure. 

Ruelle, J. A., Tsinman, 0., Avdeef, A. Acid-base cosolvent method for determining aqueous permeability of amiodarone, itraconazole, tamoxifen, terfenadine and other very insoluble molecules. Chem. Pharm. Bull. 2004, 52, 551-555. 

The cosolvent method, also known as solvent injection method permits vesicle formation for glassy or crystalline block copolymers. As a rule, the amphiphilic copolymer is dissolved in an appropriate organic solvent or solvent mixture, the role of which is to lower the Tg below room temperature next the solution is added dropwise to an aqueous buffer under vigorous stirring. Originally this method has been employed for PS-PAA and PS-PEO copolymers that self-assembled in vesicular structures by adding water to DMF or dioxane polymer solution [61,105] and then further applied to many other polymer systems [165],... 

The cosolvent method is known to result in a dispersion of vesicles of a rather broad size distribution. The polydispersity can be reduced by repeated extrusion [83], A drawback of the method is that organic solvent could remain in the vesicles and the surrounding liquid. To exclude residual solvent, the vesicle suspension is dialyzed or ultrafiltered. 

The o/w cosolvent method When the drug is not soluble in the main organic solvent, a second solvent called cosolvent is necessary to dissolve the drug. 

Polymersome dispersions were produced following two different routes, the cosolvent method and the rehydration method ... 

The encapsulation of a larger hydrophobic model substrate was successfully realized utilizing highly fluorescent QDs. The enclosing of these nanoparticles inside the PB-h-PEO polymersomes was performed only via the film rehydration procedure because the preferred dispersant of QDs, chloroform, is immiscible with water and therefore not suitable for the cosolvent method. The rehydration procedure for QDs was done analogously to that for the Nile Red samples. Afterwards, filtration through 0.45-pm filters ensured a smaller vesicle size regime, which is important for further characterization. Absorption and emission spectra indicated the presence of QDs in the vesicle solution after filtration (Fig. 65). 

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