Particulate matter small-volume injectable

Particulate matter is defined in the USP as extraneous, mobile, undissolved substances, other than gas bubbles, unintentionally present in parenteral solutions. Test methods and limits for particulates are stated in the USP for large-volume injections and small-volume injections. 

Particulate matter. When tested according to the general procedure <788>, meets the requirements under small volume injection. 

The USP 24 requirements for particulate matter in injections, small-volume injections must be fulfilled. The contamination with particles during the filling step should be equivalent at all available machines. 

Small-Volume Parenterals Color, clarity of solutions, particulate matter, pH, sterility, endotoxins. Powders for injection solutions include clarity, color, reconstitution time and water content, pH, sterility, endotoxins/pyrogens, and particulate matter. Suspensions for injection should include additional particle size distribution, redispersability, and rheological properties. Emulsion for injection should include phase separation, viscosity, mean size, and distribution of dispersed globules. 

Sterility, freedom from pyrogens, and acceptably low level of extraneous particulate matter are critical quality attributes of all injectable products. Additional critical quality attributes depend on the clinical use of the product. For example, for IV, IM, and SC routes, isotonicity and physiological pH (7.4) are always desirable in order to minimize potential irritation upon injection. Other factors may preclude this, however. If the required dose of drug must be administered in a small volume, it may not be feasible to formulate an isotonic solution. Likewise, solubility or stability considerations may preclude formulation at physiological pH. This explains why formulation pH for injectable drugs varies from about pH 2 to about pH 11. 

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

Parenteral products can be divided into two general classes according to the volume of the product. All parenteral products are sterilized and must meet all the requirements for sterility and particulate matter and must be pyrogen-free. They must be prepared using strict sanitation standards in environmentally controlled areas by individuals trained to meet these standards. The injections are overfilled with a small excess over the labeled volume to ensure that the... 

If it is not clear whether the reaction pH is correctly adjusted to around 11.5 by addition of the borate buffer, the use of an internal standard is recommended. Tlris especially holds true if hydrolysates are to be analysed. Although small amounts may be present in particulate matter, non-protein amino acids such as a-amino butyric acid or norleudne should be employed, the former having the advantage of being well separated in the HPLC system under discussion (Fig. 26-4). The internal standard should be added before the reagent. The amount added depends upon the type of analysis to be carried out and may vary from 25 to 500 pmol per injection volume. Variations in the response of the internal standard compared with a calibration run allow correction for differences in reaction pH, time and temperature. However, if these parameters have been kept constant for both calibration and sample analyses, the response should be reproducible to within about 2 %. 

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