Small-volume injectable liquids

Small-volume injectable liquids are primarily aqueous solutions. However, because many important therapeutic agents are poorly soluble or totally insoluble in water, oily solvents and water-miscible cosolvents are used to produce ready-to-use solutions. 

Solubilizing all or part of a sample matrix by contacting with liquids is one of the most widely used sample preparation techniques for gases, vapors, liquids or solids. Additional selectivity is possible by distributing the sample between pairs of immiscible liquids in which the analyte and its matrix have different solubilities. Equipment requirements are generally very simple for solvent extraction techniques. Table 8.2 [4,10], and solutions are easy to manipulate, convenient to inject into chromatographic instruments, and even small volumes of liquids can be measured accurately. Solids can be recovered from volatile solvents by evaporation. Since relatively large solvent volumes are used in most extraction procedures, solvent impurities, contaminants, etc., are always a common cause for concern [65,66]. 

In cases of severe acute asthmatic attacks, bronchodilators and steroids for direct dehveiy to the lungs may be needed in large doses. This is achieved by direct inhalation via a nebulizer device this converts a liquid into a mist or fine spray. The dmg is diluted in small volumes of Water for Injections BP before loading into the reservoir of the machine. This vehicle must be sterile and preservative-fiee and is therefore prepared as a terminally sterilized unit dose in polyethylene nebules. 

In the past decade, several novel solvent-based microextraction techniques have been developed and applied to environmental and biological analysis. Notable approaches are single-drop microextraction,147 small volume extraction in levitated drops,148 flow injection extraction,149 150 and microporous membrane- or supported liquid membrane-based two- or three-phase microextraction.125 151-153 The two- and three-phase microextraction techniques utilizing supported liquid membranes deposited in the pores of hollow fiber membranes are the most explored for analytes of wide ranging polarities in biomatrices. This discussion will be limited to these protocols. 

Chen [8] studied mixtures of the pure surfactants Ci2(EO)4 and sodium dodecyl sulfate (SDS) at 30 °C. At this temperature the former is a liquid which does not dissolve in water (see Fig. 3), and the latter is a solid. The SDS was doubly recrystallized from ethanol to remove n-dodecanol and other impurities. The solubility of SDS in pure Ci2(EO)4 at 30 °C was found to be approximately 9 wt. %. When small drops of an 8 wt. % mixture were injected into water at 30 °C, complete dissolution was observed, the time required being a linear function of the square root of initial drop radius. For instance, a drop having an initial radius of 70 (xm required approximately 100 s to dissolve, significantly more than the 16 s cited above for a slightly larger drop of pure Ci2(EO)6. Behavior was similar to that of nonionic mixtures below their cloud points discussed previously in that most of the drop dissolved rapidly, but the final small volume dissolved rather slowly with some observable emulsification. 

The purpose is to provide the USP criteria for the monitoring of liquid-borne particulate matter in injections (large- and small-volume parenterals). 

A retention gap is used to improve peak shapes under certain conditions. If you introduce a large volume of sample (>2 pL) by splitless or on-column injection (described in the next section), microdroplets of liquid solvent can persist inside the column for the first few meters. Solutes dissolved in the droplets are carried along with them and give rise to a series of ragged bands. The retention gap allows solvent to evaporate prior to entering the chromatography column. Use at least 1 m of retention gap per microliter of solvent. Even small volumes of solvent that have a very different polarity from the stationary phase can cause irregular solute peak shapes. The retention gap helps separate solvent from solute to improve peak shapes. 

Parenteral. Given by injection—include liquids, large-volume parenter-als, and small-volume parenterals (powders). 

The TDU equipment (commercially available from Gerstel GmbH, Miilheim an der Ruhr, Germany) is fully automated and connected on-line to a GC equipped with a programmable temperature vaporizer (PTV) injector for simultaneous cryotrapping of the analytes before injection. Another approach for analyte desorption is to place the stir bar in a small volume of a conventional HPLC liquid (or mobile phase) for HPLC analysis. The SBSE stir bars are trademarked as Twisters they can also be purchased from Gerstel. For more detailed information on SBSE technology, the reader is referred to two recent review articles.44 45... 

For the access of the adsorption isotherm, the volumes injected are in very small quantities less than 0.1 /jL of gaseous probes for the infinite dilution, and in the range of 0.1 fjL to about 10 fiL of liquid probes for the finite dilution up to the saturation of the adsorbate (or, up to the increase of net retention time when the quantity adsorbed increased) in the chromatography, on account of the sensitivity of detector. In the chromatographic approach, the peak maxima method [115] is generally used to determine the net retention volumes, which are corrected by the compressibility, temperature as well as flow rate, as shown in Fig. 13. 

Nonsolids The package must prevent the entry of organisms for example, packaging of sterile products must be absolutely microorganism proof—hence the continued use of glass ampules. Liquid injections are classified as small-volume parenterals (SVPs), if they have a solution volume of 100 mL or less, or as LVPs, if the solution volume exceeds lOOmL [10]. Liquid-based injectables may need to be protected from solvent loss. 

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