Karl Fisher analysis

Polymerization of styrene in each of the three types of microemulsions was performed using a water soluble initiator, potassium persulfate (K2S208), as well as an oil-soluble initiator, AIBN. As desired, solid polymeric materials were obtained instead of latex particles. In the anionic system, the cosolvent 2-pentanol or butyl cellosolve separates out during polymerization. Three phases are always obtmned after polymerization. The solid polymer was obtained in the middle with excess phases at the top and bottom. GC analysis of the upper phase indicates more than 80% 2-pentanol, while Karl-Fisher analysis indicated more than 94% water in the lower phase. Some of the initial microemulsion systems have either an excess organic phase on top or an excess water phase as the bottom layer. GC analysis showed the organic phase to be rich in 2-pentanol. However, the volume of the excess phase is much less in the initial system than in the polymerized system. 

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. 

The y-form is known to be anhydrous, and contains minimal water. The USP water specification for sorbitol requires that a sample contain less than or equal to 1.0% water in the sample [1]. The thermogravimetry (TG) and Karl Fisher (KF) data for the y-form sorbitol samples analyzed in this study are summarized in Table 4. TG analysis indicated the existence of minimal volatile content in the samples, indicating that the materials were anhydrous. The volatile component was identified as water, based on the KF values obtained for the samples. 

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]. 

Methods of Analysis. Water Content of Fractions. A chromatographic method was employed using a glass column (6 ft x 0.2 mm ID) packed with Po-rapak QS. The chromatographs used were a Varian 3700 or a Hewlett Packard 5880. Water contents were also determined by the Karl Fisher method by Huffman Laboratories, Golden, Colorado. 

Analytical Procedures. Standard methods for analysis of food-grade adipic acid are described in the Food Chemicals Codex (see Refs, in Table 8). Classical methods are used for assay (titration), trace metals (As, heavy metals as Pb), and total ash. Water is determined by Karl-Fisher titration of a methanol solution of the acid. Determination of color in methanol solution (APHA, Hazen equivalent, max. 10), as well as iron and other metals, are also described elsewhere (175). Other analyses frequently are required for resin-grade acid. For example, hydrolyzable nitrogen (NH3, amides, nitriles, etc) is determined by distillation of ammonia from an alkaline solution. Reducible nitrogen (nitrates and nitroorganics) may then be determined by adding DeVarda s alloy and continuing the distillation. Hydrocarbon oil contaminants may be determined by ir analysis of halocarbon extracts of alkaline solutions of the acid. 

In its simplest form, the Karl Fisher titration is a one-point determination of moisture content. The principal advantage is specificity for water. It is also a non-thermal method, which is very sensitive and can be easily automated. The main disadvantage is that the solid must dissolve in the titration medium to be sure that the total amount of moisture is released. If the analysis is carefully designed in such a way that moisture is extracted from the solid to the same degree each time, accurate and reproducible results can be obtained for solids that do not dissolve. 

The influence of sorbed moisture on chemical stability and the flow and compaction of powders and granulations is well established. The moisture content and hygroscopicity of excipients is particularly important as total product processing as well as finished product stability can be affected. Hygroscopicity, moisture-sorption isotherms, and equilibrium moisture content can be determined by thermogravimetric analysis and Karl Fisher titration methods. 

The stability and suitability of the formulations also needs to be determined, for example, whether the viscosity of the formulation is suitable for the administration route and is stable over time. The water content is a parameter that often has a direct influence on the stability of solid formulations and may influence the appearance of freeze-dried products immensely. Karl-Fisher titration, thermogravitometric analysis (TGA), or DSC is normally used to determine the water content. Various microscopic techniques, where both macroscopic and microscopic appearance of formulation can be determined, such as particle appearance by scanning electron microscopy (SEM) or transmission electron microscopy (TEM), are usually only needed for special formulation. There are several other methods, but which one to choose depends entirely on the formulation and the critical parameters (149,150). 

The product was dried prior to element analysis (in vacuo over P2O5,18 h at 69°C). No crystal water was present (Karl-Fisher). 

The extraction of phosphates from freshly cut plants containing different amounts of water at the surface of leaves or within other material could be a source of uncertainty in the analysis step. With this in mind, one solution is to freeze-dry the fresh plant material. The dried material can then be milled to a fine powder, and the content of water is determined by the Karl-Fisher method, as modified by Moibroek and Shahwecker. Finally, analyte anions can be extracted from the plant material in accordance with the AOAC method for dried vegetables and flours. " ... 

The experiment involves periodic sampling of the solution in the reaction flask. With a syringe, a sample is extracted for ethanol analysis in a calibrated gas chromatograph (Bendix 2600 with 6 foot Porapak S column). At the same time, the solution is titrated with Karl Fisher reagent to give semiquantitative water analysis. The data collected are plotted in Figure 2. 

Analysis. Free fatty acids were ethylated in ethanol dehydrated with molecular sieves using gaseous HCl as the catalyst. Ethyl esters of fatty acids were analyzed on a DB-23 capillary column (0.25 mm x 30 m J W Scientific, Folsom, CA) connected to a Hewlett-Packard 5890 gas chromatograph (Avondale, PA) as described previously (19). The water content in the oil layer was determined by Karl Fisher titration (moisture meter CA-07 Mitsubishi Chemical, Tokyo, Japan). The contents (by weight) of free fatty acids and fatty acid ethyl esters were analyzed by a thin-layer chromatography/flame ionization detector... 

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. 

Powder X-ray diffraction solid-state NMR spectroscopy Raman/IR spectroscopy thermal analysis Solution NMR spectroscopy elemental analysis Karl-Fisher titration evolved gas analysis... 

---