Karl Fisher measurements

The Karl Fisher measurements of the heated evacuated powder yield a total water content of 3.73 wt%, while an exposed powder has a total water concentration of 5.72 wt%. Titration measurements indicate that the physi sorbed water content of the heated evacuated powder is 1.73 wt%. Thus, the remaining 2.00 wtX corresponds to the concentration of Si-OH sites. This is considered to be in good agreement with the weight gain data (described above). 

Water can be identified from its physical properties. Also, trace amounts of water may be determined by Karl-Fischer analysis. The Karl-Fisher reagent is a solution of iodine, sulfur dioxide and pyridine in methanol or methyl cel-losolve. Water of crystallization in hydrates can be measured by TGA and DTA methods. The presence of trace moisture in gases can be determined by mass spectrometry. The characteristic mass ion is 18. 

There are three ways to obtain the total solid (1) determine the water content by Karl Fisher titration, (2) weigh an evaporate portion of product, or (3) sum up all the ingredients, including mometasone furoate and phenylethyl alcohol, which are stated (claimed) on the label. The combination of all three measurements generally gives quite an accurate estimation of the total solid and total cellulose ... 

The performance verification of Karl Fisher apparatus should include checks for the accuracy and precision of the instrument. The linearity of the instrument should be determined at installation. The first step is to standardize the instrument (see Section 14.3.2) pure water is sufficient for this purpose. Sodium tartrate dihydrate standard (water content 15.66 0.05%) can be used to assess the accuracy, precision, and linearity of the instrument. Typically, one would measure the water content of at least five samples, over the intended instrument user range. For example, the water content of sodium tartrate dihydrate samples that were 65 mg (ca. 10 mg H20), 195 mg (ca. 30 mg H20), 325 mg (ca. 50 mg H20), 455 mg (ca. 70 mg H20), and 650 mg (100 mg H20) could be determined. Calculate the percent water to assess the instrument s accuracy. The results should be within 98 to 102% of 15.66% water. Determine the % RSD of the percent water found to assess the precision of the instrument. The % RSD should be less than or equal to 1%. Finally, plot the expected water content versus the percent water content to assess the linearity of the instrument s response. A correlation coefficient (r) value of 0.999 or greater is acceptable. 

The analytical method for moisture determination must be validated before use during process validation studies. There are numerous techniques for moisture analysis that range from physical methods, such as loss on drying, to chemical methods, such as Karl Fisher titration. A comparative review of the conventional techniques are presented in an overview [32], The measurement of residual moisture is lyophilized pharmaceuticals by near-infrared (NIR) spectroscopy has recently been expanded [33]. 

Water concentrations in liquid and solid phases were measured by the Karl Fisher method using the Karl Fisher Titrator (Mettler DL 18). Butanol and butyl butyrate were determined by gas chromatography using a 6-ft, 5% DEGS on a Chromosorb WHP, 80/10 mesh column (Hewlett Packard, Palo Alto, CA) and hexanol as internal standard. Acid consumption was monitored by volumetric titration of samples diluted in ethanol employing 0.02 M KOH alcoholic solution and phenolphthalein as pH indicator. Esterification was expressed as molar percent of consumed reactant, according to Eq. 1 ... 

The water contamination level in solutions is usually measured by Karl Fisher (KF) titration. The water detection is based on the mechanism described below. In brief, the reaction includes two steps ... 

The xylenes (EM Science) were dried over 4 A molecular sieves. Residual water content < 20 pg/mL by Karl Fisher titration. The checkers dried hexanes (Fisher Scientific Company), tetrahydrofuran, and xylenes over 4 A molecular sieves. The checkers did not measure the residual waler content of the solvents. 

Numbers in square brackets indicate water content values measured adopting the Karl Fisher method. 

The characterization of the total mass thus obtained, performed on representative samples taken during the vial filling procedure, gave additional information on the properties of the material. The average moisture content, measured by Karl-Fisher titration, was lower than 3%. The particle size distribution of the whole mass, measured using the Sympatec analyzer with Helos measuring device, was to peak at 80-90 pm with an upper limit of 435 pm. 

Karl Fisher Coulometer Metrohm, Model 737 (Herisau, Switzerland) was employed to measure the water content of the samples. 

Thermogravimetry measures the weight change of a sample as a function of temperature. A total volatile content of the sample is obtained, but no information on the identity of the evolved gas is provided. The evolved gas must be identified by other methods, such as gas chromatography, Karl Fisher titration (specifically to measure water), TG-mass spectroscopy, or TG-infrared spectroscopy. The temperature of the volatilization and the presence of steps in the TG curve can provide information on how tightly water or solvent is held in the lattice. If the temperature of the TG volatilization is similar to an endothermic peak in the DSC, the DSC peak is likely due or partially due to volatilization. It is usually necessary to utilize multiple techniques to determine if more than one thermal event is responsible for a given DSC peak. 

Numerous methods for the determination of monomer purity, including procedures for the determination of saponification equivalent and bromine number, specific gravity, refractive index, and color, are available from manufacturers (68—70). Concentrations of minor components are determined by iodimetry or colorimetry for HQ or MEHQ, by the Karl-Fisher method for water, and by turbidity measurements for trace amounts of polymer. 

Different properties of the prepared dry adsorbed emulsions were examined (yield value, deteiminadon of dry content, measurement of angle of repose, deter-iiiinatlou of flow rate, density, bulk density, percentage of porosity, particle size analysis. Karl Fisher titrimetry. drug release study, stability study) and the most appropriate selected for in vivo investigation. 

The percentages of water content in cyclohexane and Triton X-45 were measured with titrator ( Mettler Toledo DL38, Karl Fisher Titrator) from Virginia. The particle size and electrophoretic mobility were determined by using zetasizer series nano-ZS, Malvern Instrument from United Kingdom. Stirrer of HTS-1003 LMS was used. 

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