For solubility determination

Avdeef, A., Berger, C. M. pH-metric solubility. 3. Dissolution titration template method for solubility determination. Eur. J. Pharm. Sci. 2001, 14, 281-291. 

A reference solution is prepared by a dilution method. A known quantity of sample is dissolved in a known volume of the system buffer of known pH the amount of sample is X times less than in the above case in order to avoid precipitation in the formed solution. The spectrum is immediately taken by the UV spectrophotometer, to take advantage of the possibility that solution may be supersaturated (i.e., solid should have precipitated, but because not enough time was allowed for the solid to precipitate, the solution was temporarily clear and free of solid). Mathematical treatment of the spectral data yields the AUC of the reference sample solution, AUQ . The ratio R = AUCS/AUCS is used to automatically recognize the right conditions for solubility determination when the reference has no precipitate, and the sample solution is saturated with precipitate. Under these conditions, solubility is determined from the expression... 

Conditions used for solubility determinations Pressure PSI Temp. °C... 

Figure 6.24 compares the amounts of solvent required to analyze 24 compounds for solubility determination employing a four-point calibration and duplicate analysis when traditional HPLC and... 

FIGURE 6.24 Amount of solvent needed for solubility determinations employing HPLC and /iPLC (24 compounds, 4-point calibration curve, duplicate analysis). 

FIGURE 6.25 Comparison of techniques employed for solubility determination. 

Bhattachar et al.45 used CLND for solubility determinations and compared results to those obtained from UV spectrophotometry and HPLC. CLND has a throughput of 96 compounds per day with a reduced compound consumption of approximately 3 mg. The sensitivity of the instrument is approximately 6.25 pg/mL for a compound with a molecular weight of 350 and 4 nitrogens per molecule. 

Bhattachar, S.N., Wesley, J.A., and Seadeek, C. 2006. Evaluation of the chemiluminescent nitrogen detector for solubility determinations to support drug discovery. J. Pharm. Biomed. Anal. 41 152. 

A review of the commonly used experimental methods for solubility determinations is presented in Table 1. Briefly, batch equilibration is the conventional method of preparing saturated solutions for solubility determinations, where an excess amount of solute chemical is added to water and equilibrium is achieved... 

Inherent viscosities of the polymers were determined at a concentration of 0.23 gram/100 ml in 60/40 phenol/tetrachloroethane at 25 °C. Polyesters for solubility determinations were prepared by conventional... 

The HPLC method development requirements using short columns and fast HPLC to determine the assay concentration for each polymorph at the different temperatures are the same as for solubility determination. However, for stability evaluation of the different polymorphs a stability-indicating HPLC method should be used. 

Determination of solubility under assay conditions can help optimize assay protocols for biological screening and HTS. The samples for solubility determination in bioassay buffers are typically prepared step-by-step according to bioassay protocols. The solutions are then centrifuged and the supernatants are assayed using LC-MS against a fully soluble standard in solvent. The data can be used iteratively on a set of structurally diverse compounds to guide assay development and maximize solubility. 

Concentrating method Scale Benefits Lunitations Used for solubility determination... 

The solubility of a material is usually determined by the equilibrium solubility method, which employs a saturated solution of the material, obtained by stirring an excess of the material in the solvent for a prolonged period until equilibrium is achieved. Common solvents used for solubility determination are ... 

Naumann and Reinhardt [329] described the use of the radioactive marker method to determine the oxide solubilities. The advantages of this method concern only the procedure for the subsequent treatment of the obtained sample of the melt with the metal oxide, whereas its drawbacks are similar to those of the classic isothermal saturation methods. This radiochemical method has not been used extensively for solubility determinations in molten salts. 

The p and T conditions chosen for solubility measurements with the dynamic method were limited by the temperature stability of the fiber optic system. The maximum temperature was 70 °C at a maximum pressure of 250 atm. In Figure II eight p/T- conditions for solubility determinations are presented. 

It requires only a small amount of samples (0.2-0.5mg for two pHs for assay range of 0.5-200 mg/mL), making possible for solubility determination for early researeh eompounds with limited sample amount. 

PEG differs from other polymers commonly used in glass solutions. Depending on the chain length, it may be liquid or solid at room temperatures, thus allowing different approaches for solubility determination. Thermal analysis together with the Fox equation was used to determine the solubility of six drugs in PEG 400, which is a... 

Figure 13 Schematic diagram of apparatus for solubility determination by method of sampling with temperature and pressure drops (The Experimental Determination of Solubilities, Vol 6, Hefter Tomkins).

Figure 1.6 Schematic diagram of flexible cell system for solubility determination at elevated pressure by method of sampling (The Experimental Determination of Solubihties, Vol 6, Hefter Tomkins. Dickson, F.W., Blount, C.W. andTunell, G. (1963) Amer. J. Sci., 261, pp. 61-78 Blount, C.W. and Dickson, F.W. (1969) Geochim. Cosmochim. Acta, 33, pp. 227 245.).

Rejerences. — For solubility determinations Goodwin, Zeitsckr. physikal. Chan., 1894, 18, 577 Ab and Cox, ibid, 1903, 46, i. For stability of complex ions Bod nder and Fittig, Zeittehr. fhysikal. Chan., 1902,39,597. For determinations of hydrolysis of salts Denham, Trans. Chan. Soc., 1908, 93, 41. For decomposition potentials Bennewits, Zeitschr, yhysikal. Chan., 1910, 72, 202. 

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