Surfactants parenteral preparations

Surfactants such as polysorbates may be used as solubilising agents. Polysorbate 80 has been associated with the E-Ferol syndrome (thrombocytopenia, renal dysfunction, hepatomegaly, cholestasis, ascites, hypotension and metabolic acidosis) in low-birthweight infants when used as a solubiliser aid in parenteral preparations. 

An additional application of surfactants in parenteral preparations is the transport of drug particles via blood-brain barrier, the membrane that protects the brain from toxic substances, assimilating only nutrients. The drug is bound to polymeric nanoparticles having the average diameter of 270 30 nm, and the resulting nanoparticle-drug complex is coated with a surfactant, such as... 

Flubiprofen o/w ME systems were prepared and evaluated as vehicles for parenteral drug delivery [114]. These systems were formulated using POE 20 sorbitan mono-laurate (Tween 20) as the surfactant and ethyl oleate as the oil phase. Flubiprofen... 

Vineland, NJ) or over-the-counter cosmetic creams promoted for improved hydration (L Oreal, Paris and Dior, Paris). More recently, parenteral liposome formulations of amphotericin B, doxorubicin, and dau-norubicin have been approved and marketed (ABELCET, Elan, the Liposome Co., Inc, Princeton, NJ AmBisome and DaunoXome, Nexstar/Fujisawa, Deerfield Park, IL Amphotec and Doxil, Sequus/ Alza, Menlo Park, CA), with others on the horizon for applications in photodynamic therapy. Although the vast majority of liposome preparations are constructed from phospholipids, other nonphospholipid materials can be used either alone or in mixtures to form bilayer arrays. One such example is Amphotec, which utilizes sodium cholesteryl sulfate as the primary lipid. Other liposome forming materials may include but are not limited to fatty-acid compositions, ionized fatty acids, or fatty acyl amino acids, longchain fatty alcohols plus surfactants, ionized lysophospholipids or combinations, non-ionic or ionic surfactants and amphiphiles, alkyl maltosides, a-tocopherol esters, cholesterol esters, polyoxyethylene alkyl ethers, sorbitan alkyl esters, and polymerized phospholipid compositions. ° ... 

The use of surfactants in parenteral products is limited by their potent side-effects. All surfactants, especially those that are ionic may cause hemolysis. Anaphylactoid reactions have been noted, particularly in association with the destruction of lymphocytes, resulting in histamine release. Phospholipids are generally well-tolerated, and are frequently used in the preparation of emulsions. Nonionic surfactants such as Cremophor EL and polysorbate 80 (Tween 80) are known to cause hypersensitivity reactions (Eschalier et al., 1988 Mounier et al., 1995 Theis et al., 1995 Munoz et al., 1998 Volcheck and Van Dellen, 1998), including hypotension, largely via histamine release mechanisms. Because of potential side-effects, it is now traditional to pretreat the patient with an antihistamine and possibly a corticosteroid (e.g., prednisone) before administration of formulations that contain Cremophor EL. 

Cationic surfactants are bactericidal agents and are used as antiseptics and disinfectants in topical and other external preparations and are never used in parenterals. Lecithins and other natural phospholipids, as one of the main constituents... 

Typical excipients used in parenteral suspensions include surfactants that are used to stabilise emulsions and suspensions as wetting agents (polysorbate 80, poloxamer), as micelle makers for the preparation of solubilisations and to influence the flocculation and deflocculation behaviour of a dispersed system (carmellose sodium, polyvidone). Paren-terally used surfactants in high concentrations are toxic and may cause venous irritation and occasional thrombophlebitis. However, these high concentrations are not necessary to formulate stable parenteral suspensions. 

Amphoteric surfactants possess both an anionic and a cationic function. In small-scale preparation they are little used but their role may increase in the future. Examples are long chain betains and phospholipids (e.g. lecithin). Phospholipids play an important role as emulsifiers and micelle formers for parenteral emulsions (see Sect. 13.5.7) and micellar solutions and also in liposome technology. 

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