Small volume parenterals

Large-volume parenterals (LVPs) and small-volume parenterals (SVPs) containing no antimicrobial agent should be terminally sterilized. It is common practice to include an antimicrobial agent in SVPs that cannot be terminally sterilized or are intended for multiple-dose use. The general exceptions are products that pass the USP Antimicrobial Preservative Effectiveness Test [1] because of the antimicrobial activity of the active... 

USP Type II can be used for products that remain below pH 7.0 for their shelf life. The suitability of Type II for small volume parenterals should be evaluated for unbuffered solutions on a case-by-case basis. Type II containers are frequently found to be suitable for a variety of large-volume parenterals due to the less stringent requirements imposed by their lower surface-to-volume ratios. 

Glass containers for small volume parenteral products Factors for selection and test methods for identification. Parenteral Drug Association Inc., Technical Methods Bulletin No. 3, 1982. 

Small-volume parenterals Appearance, color, particulate matter, dispersibility (suspensions), pH, sterility, pyrogenicity, and closure integrity... 

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

TITLE Visual Inspection of Small-Volume Parenterals... 

The purpose is to provide criteria for accepting or rejecting small-volume parenterals during visual inspection. 

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. 

CSP Chemical sterilization process SVL Small volume parenterals (lyophilized)... 

CTL Control testing laboratories SVT Terminally sterilized small volume parenteral... 

Harwood, R. J., Portnoff, J. B., and Sunbery, E. W. (1993) The processing of small volume parenterals and related sterile products, Pharmaceutical Dosage Forms Parenteral Medicati,o(te E. Avis,... 

DeLuca, P.P., Boylan, J. C. Formulations of small volume parenterals. In Avis, K. E., Lachman, L., Liberman, H. A. eds. Pharmaceutical Dosage Forms Parent-erial Medications, Vol. 1. New York Marcel Dekker, 1984, p. 195. 

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

Small Volume Parenterals (SVP) Appearance, color, clarity (particulates), pH, and sterility checks at reasonable intervals are minimum standards. Powders for reconstitution should also include residual moisture and stability checks after reconstitution. Except for ampules, upright and inverted storage of final product should also be evaluated. 

In addition to their use in large-volume parenterals and IV sets, thermoplastic polymers have also recently found utility as packaging materials for ophthalmic solutions and some small-volume parenterals [43], However, there are many potential issues with using these polymers as primary packaging components that are not major concerns with traditional glass container closure systems, including [44] ... 

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. 

Kvarnstrom, A.C. Ernerot, L. Mattsson, K. Form-Fill-Seal Experience with the Aseptic Filling and Terminal Sterilization of Small Volume Parenterals, Proceedings of PDA International Congress, 1992, 180. 

The use of cosolvents in small-volume parenteral preparations is often critical due to the limited volume of solution that can be administered by a single injection. Thus, the required dose of drug must often be incorporated in 1 or 2mL of solution. Table 6 lists parenteral products containing cosolvents. The cosolvents most often used include ethanol, propylene glycol, glycerin, PEG 400, and, sometimes, dimethylacetamide. Other cosolvents, such as DMSO, have been used as solvents for parenteral formulations of experimental anticancer agents however, their use is restricted due to toxicity and potential incompatibilities with plastic administration devices. ... 

Baxter Healthcare http //www.baxter.com Large and small volume parenterals, premix medications, reconstitution products and accessories, syringe pumps and sets, interlink, administration sets, infusion pumps... 

Endotoxins and foreign particulates are consistent with limits for small volume parenteral products. 

Table 2 Small-volume parenteral products containing oil(s) as the solvent system...

Table 5 Antimicrobial preservative agents in small-volume parenterals...

Table 6 Common buffer systems used in small-volume parenteral products...

Boylan, J.C. DeLuca, P.P. Formulation of small volume parenterals. In Pharmaceutical Dosage Forms Parenteral Medications, 2nd Ed. Avis, K.E., Lieberman, H.A., Lachman, L., Eds. Marcel Dekker, Inc. New York, 1992 ... 

Aluminum in large and small volume parenterals used in total parenteral nutrition. Federal Register January 5 1998, 63 (2), 176-185. 

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