Benzyl alcohol as preservative

Lorazepam Ativan (Wyeth) hypnotic, anticonvufsan t 18% PEG 400 in propylene glycol, with 2% benzyl alcohol as preservative 166-168 2.48 (Avdeef, 2003)... 

Each 1 mL of single dose solution contains 2000, 3000, 4000 or 10,000 units of Epoetin alpha, 2.5 mg of albumin (human), 5.8 mg of sodium citrate, 5.8 mg of sodium chloride, and 0.06 mg of citric acid in water for injection, LISP (pH 6.9 0.3). This formulation contains no preservative. The 2-mL (20,000 units, 10,000 units/mL) multidose vial, each 1 mL of solution contains 10,000 units of Epoetin alpha, 2.5 mg of albumin (human), 1.3 mg of sodium citrate, 8.2 mg of sodium chloride, 0.11 mg of citric acid, and 1% benzyl alcohol as preservative in water for injection, LISP (pH 6.1 0.3). 

Many of these reactions are related to the quantity of excipient found in a dosage form. Benzyl alcohol benzalkonium chloride, propylene glycol, lactose, and polysorbates are all associated with dose-related toxic reactions [52-54], Large-volume parenterals containing 1.5% benzyl alcohol as a preservative have caused metabolic acidosis, cardiovascular collapse, and death in low birth weight premature neonates and infants. The cumulative dose of benzyl alcohol ranged from 99 to 234 mg/kg per day in these patients [55,56], Dose-related adverse effects to excipients are of particular concern in the preterm, low birth weight infant because... 

Bacteriostatic sodium chloride Do not use in newborns. Benzyl alcohol as a preservative in bacteriostatic sodium chloride injection has been associated with toxicity in newborns. These solutions have not been reported to cause problems in older infants, children, and adults. 

Benzyl alcohol The multiple-dose vials of dalteparin, enoxaparin, and tinzaparin contain benzyl alcohol as a preservative. Benzyl alcohol has been associated with a fatal gasping syndrome in premature infants. Because benzyl alcohol may cross the placenta, do not use LMWHs preserved with benzyl alcohol in pregnant women. Thromboembolic events If thromboembolic events occur despite LMWH prophylaxis, discontinue and initiate appropriate therapy. 

Some preservatives can cause injection site reactions, which is another factor that needs consideration when choosing a preservative. In clinical trials that focused on the evaluation of preservatives and buffers in Norditropin , pain perception was observed to be lower in formulations containing phenol and benzyl alcohol as compared to a formulation containing m-cresol (69). Interestingly, among the commonly used preservatives, benzyl alcohol possesses anesthetic properties (70). 

To be reconstituted with 5 mL bacteriostatic 0.9% sodium chloride for injection, USP, with normal 0.9% benzyl alcohol as a preservative saline (pH in the range of 7.0-9.0) Per vial 30 mg mannitol SC... 

Vials HSA containing formulation 0.25% albumin (human) sodium chloride sodium citrate citric acid 0.9% benzyl alcohol as a preservative water for injection... 

Interferon alfa-2a formulations contain excipients sodium chloride, polysorbate, ammonium acetate, and benzyl alcohol as a preservative. Interferon alfa is also approved for use in the treatment of several other disorders. 

This ester-type anesthetic contains butacaine, with benzyl alcohol as a preservative. It is available as an ointment. The maximum dose is 5 ml of a 4% solution or 200 mg. 

The use of benzyl alcohol as a local anesthetic was previously discussed. It is also used as a preservative in parenteral dosage forms. However, there is some evidence that benzyl alcohol is neurotoxic and its use is contraindicated in the United Kingdom in children under 3 years of age. ° ... 

Allergic contact dermatitis, characterized by erythema, palpable edema, and raised borders, was attributed to benzyl alcohol (2). In this case, the benzyl alcohol was present as a preservative in an injectable solution of sodium tetradecyl sulfate, a sclerosing agent used for the treatment of varicose veins. The author provided a hst of 151 injectable formulations (48 for subcutaneous administration) that contained benzyl alcohol as a preservative in the range 0.5-2.0%. The list included hormones and steroids, antihypertensive drugs (reserpine), vitamin formulations (vitamins B12 and Bg), ammonium sulfate, antihistamines, antibiotics, heparin (17 brands), tranquillizers, and sclerosing agents (sodium morrhuate and sodium tetradecyl sulfate). 

The fatal toxic syndrome in low-birth-weight neonates, which includes symptoms of metabolic acidosis and respiratory depression, was attributed to the use of benzyl alcohol as a preservative in solutions used to flush umbilical catheters. As a result of this, the FDA has recommended that benzyl alcohol should not be used in such flushing solutions and has advised against the use of medicines containing preservatives in the newborn. ... 

Each milliliter contains 3 MIL of interferon alpha-2a, recombinant, 7.21 mg of sodium chloride, 0.2 mg of polysorbate 80, 10 mg of benzyl alcohol as a preservative, and 0.77 mg of ammonium acetate. 

Vials HSA containing formulation 0.25% albumin (human) sodium chloride sodium citrate citric acid 0.9% benzyl alcohol as a preservative water for injection Pre filled syringe polysorbate-80 containing (HSA- free) formulation glycine polysorbate 80 sodium chloride sodium phosphate monobasic dihydrate sodium phosphate dibasic dihydrate water for injection... 

D. Rapid or large-volume IV administration may cause cardiotoxicity similar to that seen with phenytoin (see p 303) because of the diluent propylene glycol. Continuous infusions with this vehicle may result in a hyperlactatemia, increased osmolar gap, and renal dysfunction. Several products also contain up to 2% benzyl alcohol as a preservative. 

The solubility of 2,4-dichloro benzyl alcohol in water is poor in aqueous systems it tends to migrate into the organic phase. The use of 2,4-dichloro benzyl alcohol as a preservative therefore is very limited. Nevertheless it is listed in the EC positive list of preservatives for cosmetic products (maximum concentration for the applications 015%). Its main application, however, is in hand disinfectants. 

For example, the label of a prescription drug to be administered in the vein reads, testosterone propionate injection with benzyl alcohol as a preservative 10%, in sesame oil . Cocoa butter is a constituent of pro-menthazine hydrochloride used either orally or by suppositories for perennial and seasonal allergic rhinitis. It is manufactured by Wyeth Laboratories, Inc., Philadelphia, PA. Progesterone injection, USP, in sesame oil is used for intramuscular use only (manufactured by Steris Laboratories, Phoenix, AZ). 

Benzyl alcohol, [100-51 -6] C H CH20H (bp, 205.4°C at 101.3 kPa), produced by the hydrogenation of benzaldehyde is used in color photography as a parenteral solution preservative as a general solvent and as an intermediate in the manufacture of various benzoate esters for the soap, perfume, and flavor industries (see Benzyl alcohol and P-phenethyl alcohol). 

Benzyl alcohol (C6H5CH2OH). This has antibacterial and weak local anaesthetic properties and is used as an antimicrobial preservative at a concentration of 2%, although its use in cosmetics is restricted. 

The unfolding behavior of multidomain proteins in the presence of preservatives has also been evaluated. For example, IL-1R (type I) has three domains that correspond to three unfolding transitions as measured by microcalorimetry and depicted in Figure 13.1.31 All three transitions exhibit some shift to lower Tm in the presence of the three preservatives tested (i.e., 0.065% phenol, 0.1% metacresol, and 0.9% benzyl alcohol), in comparison to a control containing no preservative. Such a destabilization could have consequences for the shelf-life of the product. Another example of the impact of preservatives on a multidomain protein is illustrated in Figure 13.5. The protein is fused to a single IgCi, Fc. The... 

Figure 13.6 The relationship between Tm (°C) and benzyl alcohol content (obtained from the data in Figure 13.4) expressed as a percentage (w/w). Note that the relationship can be fitted to a line having a slope that describes the destabilizing force of the preservative. The dashed line designated as A illustrates a preservative force that is less destabilizing in contrast to the dashed line designated as B that is more destabilizing than benzyl alcohol.

Enbrel Enbrel is used for the treatment of rheumatoid arthritis. It is supplied as a sterile, preservative-free, lyophilized powder. The powder is reconstituted with 1 mL sterile bacteriostatic water-for-injection (containing 0.9% benzyl alcohol) prior to parenteral injection. 

Benzyl alcohol Benzyl alcohol, which is contained in some of these products as a preservative, has been associated with an increased incidence of neurological and other complications in premature infants that are sometimes fatal. 

Because of the problems encountered with the water system, the use of aliphatic alcohols, ie.g., methanol, ethanol, and isopropanol, as modifiers of the adsorption strength has been recommended (44. 45. 50. 51). Usually, between 0.01 and 0.5% (v/v) alcohol is added to the eluent. As an example, the k values for the benzyl alcohols on a silica column are in the same range when eluted with dichloromethane containing either 0.1% water (50% water-saturated) or 0.15% methanol or 0.3% isopropanol (45). The preparation and preservation of these alcohol-eluent mixtures is accompanied by problems similar to those discussed with water-modified eluents. Also, column equilibration is slow (44). The efficiency of columns operated with alcohol-modified eluents is generally lower than that of water-modulated eluent system. At some alcohol concentrations, distorted peaks with tailing or frontal asymmetry have been observed 44), but olhei workers using another silica could not verify this observa tion (61). 

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