Small-volume parenterals products

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. 

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

In nasal, and otic formulations a concentration of 0.002-0.02% w/v is used, sometimes in combination with 0.002-0.005% w/v thimerosal. Benzalkonium chloride 0.01% w/v is also employed as a preservative in small-volume parenteral products. Benzalkonium chloride was also shown to enhance the topical penetration of lorazepam. ... 

Large- and small-volume parenteral products are prepared in the pharmacy and delivered at regularly scheduled times to the patient care area 7 days/week. 

The use of Cremophore EL in the microemulsions is avoided nowadays due to several adverse effects such as anaphylactic shocks and histamine release [20 ]. The other important consideration is the concentration of surfactants and co-surfactants which should be minimal and preferably not exceed 20%. Furthermore, it is necessary to ensure that the microemulsion structure is preserved in the presence of the tonicity adjusting solutions such as 0.9% saline solution and preservatives. The parenteral microemulsions should also be able to withstand tests such as freeze-thaw cycling which ensure their physical stability. It has been shown that the colloidal carriers based on Solutol HS 15 can withstand freeze-thaw cycling very efficiently whereas lecithins can offer stability to autoclaving [ 112 ]. Cosurfactants such as benzyl alcohol cannot be used for intravenous applications but can be used for the small volume parenteral products up to the concentration of 1% w/v. Ethanol at concentrations above 10% usually results in the pain on injection. Co-surfactants such as glycofurol are reported to acceptable for parenteral products but there are no products based on glycofurol available for the human use. The pyrrolidone derivatives are reported to be acceptable for veterinary applications. 

For sterile Filtration of ophthalmics and small-volume parenteral products it is not unusual to Find several Filters mounted in series. For instance a compounded bulk product may be Filtered through the wall from a dean area into an aseptic filling room. In these cases there are usually two filters mounted in... 

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. 

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,... 

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. 

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. 

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... 

Klein GL. Aluminum in parenteral products medical perspective on large and small volume parenterals. J Parenter Sci Technol 1989 43(3) 120-4. 

The most obviously recognized sterile pharmaceutical preparations are injections. These vary from very small volume antigenic products to large volume, total parenteral nutrition products. Other... 

Blow-fill technology is an aseptic process whereby the container is formed from thermoplastic granules, filled with sterile solution and sealed, all within one automatic operation. The bulk solution should have a low bioburden and is delivered to the machine through a filling system that has been previously sanitized and steam sterilized in situ. Concern has been expressed that the machine itself may generate particles. The plastic granules are composed usually of polyethylene, polypropylene or one of their copolymers and are heat extruded at 200°C into a tube. The two halves of a mould close around this tube and seal the base. The required quantity of sterile fluid is filled into the container, which is then sealed. Products packed in this way include intravenous solutions, and small volume parenteral, ophthalmic and nebulizer solutions. The... 

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. 

Finally, a microbiological technical data section is necessary for any NDA for which a sterile claim is being made—this would include such products as large and small volume parenterals and sterile ophthalmic solutions. 

Parenteral (large and small volume) sterile products administered intravenously, intramuscularly, intrathecally,... 

Today parenteral products are divided into two types, namely large and small volume parenterals. Large volume solutions in containers of 100 ml or more are essentially for intravenous use, usually over an extended period of time. Such solutions are also for irrigation and dialysis. Small volume parenterals are for immediate injection by various routes, such as subcutaneous, intramuscular and intravenous. 

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. 

Small Volume Parenteral A sterile injectable product intended for administration under or through the skin with a nominal fill volume of 100 mi or less. It may be packaged in glass or suitable plastic material. 

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,... 

---