Small-volume parenteral dosage forms

Many drugs are administered as parenterals for speed of action because the patient is unable to take oral medication or because the drug is a macromolecule such as a protein that is unable to be orally absorbed intact due to stability and permeability issues. The U.S. Pharmacopoeia defines parenteral articles as preparations intended for injection through the skin or other external boundary tissue, rather than through the alimentary canal. They include intravenous, intramuscular, or subcutaneous injections. Intravenous injections are classified as small volume (<100 mL per container) or large volume (>100 mL per container) injections. The majority of parenteral dosage forms are supplied as ready-to-use solutions or reconstituted into solutions prior to administration. Suspension formulations may also be used,101 although their use is more limited to a subcutaneous (i.e., Novolin Penfill NOVO Nordisk) or intramuscular (i.e., Sandostatin LAR Depot Novartis) injection. Intravenous use of disperse systems is possible but limited (i.e., Doxil Injection Ortho Biotec). 

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. 

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 ... 

Parenteral dosage forms can be categorized as small-volume parenteral (SVP), large-volume parenteral (LVP), and lyophilized products. Three basic types of SVP formulations exist solution, suspension, and emulsion. The following aspects should be addressed to successfully formulate a parenteral dosage form (1) selection of a suitable vehicle (aqueous, co-solvent, or nonaqueous) (2) selection of formulation adjuvants, such as buffering agents. 

The widest range of parenteral products are however, the small volume parenterals (SVPs). These may be sterile solutions for injecting directly into the patient. They may be concentrated solutions or suspensions or emulsions or even solids (solid dosage forms may be anhydrous, crystalline, or freeze dried [lyophilized]) for dilution or reconstitution in LVPs for direct injection or infusion into the patient. 

JB Portnoff.. RJ Harwood., EW Sunbery. The processing of small volume parenteral and related sterile products. In KE Avis, L Lochman. HA Lieberman, eds. Pharmaceutical dosage forms. Vol I. Parenteral medications. New York Marcel Dekker, 1984. p 246,... 

Given the complexity of some of the dosage forms mentioned earlier, this guidance was limited to solid oral dosage forms, liquid oral dosage forms, and parenterals (small and large volume). These products serve as models, and the principles applied can be used for all other dosage forms such as inhalation products, topical formulations, and transdermal systems. 

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