Antimicrobial preservatives, drug formulations

Cetylpyridinium chloride is a quaternary ammonium cationic surfactant, used in pharmaceutical and cosmetic formulations as an antimicrobial preservative see Section 10. It is used therapeutically as an antiseptic agent used alone or in combination with other drugs for oral and throat care used in nonparenteral formulations licensed in the UK and used in oral and inhalation preparations at concentrations of 0.02-1.5 mg (see Section 16). 

Comments cationic emulsifying wax is claimed to be of particular value in cosmetic and pharmaceutical formulations when cationic characteristics are important. Thus it can be used in medicated creams, germicidal creams, ointments and lotions, hair conditioners, baby creams, and skin care products in which cationic compounds are included. Cationic emulsifying wax is compatible with cationic and nonionic materials, but is incompatible with anionic surfactants and drugs. Additional antimicrobial preservatives should be included in creams. Cetrimide may cause irritation to the eye see Cetrimide. 

Benzyl alcohol is primarily used as a solvent and an antimicrobial preservative, but it has also found use as an antiseptic and local anesthetic. It is also used as a raw material of various esters, used in the soap, perfume, and flavor industries. Acceptable daily intakes were established at 5 mg kg for benzyl alcohol by the World Health Organization. In 1998, benzyl alcohol was reported by the US Food and Drug Administration as being used in 322 cosmetic formulations, belonging to 43 cosmetic categories. 

Conversely, the addition of some other ions can promote solubility by the indifferent electrolyte effect. The use of hydrophilic molecules such as the hydroxyacids (e.g. citrate, tartaric) or aromatic carboxylic acids (e.g. benzoic) can create cavities in the water structure thereby promoting solubilization. Many salt formers increase drug solubility by this type of mechaiusm. Citrate buffers and sodium benzoate, the latter often used in formulations as an antimicrobial preservative, are known to enhance the solubility of a number of drugs. 

Ophthalmic products have to be manufactured sterile and be free from micro-organisms. Once opened, the sterility of a multidose product must be maintained during its period of use. This is usually required for at least 4 weeks, after which the product is discarded. If the drug itself does not possess antimicrobial properties, then an antimicrobial preservative must be included in the formulation to ensure that any micro-organisms accidentally introduced during use are destroyed. 

A preservative is a substance that extends the shelf-life of drug products by preventing oxidation or inhibiting microbial growth.14 Preservatives must be monitored in the products since they are considered to be active components. Generic HPLC assays are typically developed for preservatives such as buty-lated hydroxytoluene (BHT), an antioxidant for solid dosage forms, and antimicrobials such as parabens, sodium benzoate, or sorbic acid in liquid formulations. For these additive components, typical assay specifications are 85-115% of label claim. 

In the past few years, ILs gained importance for use in several pharmaceutical applications. They are found to be particularly useful for the solubilization of poorly soluble drugs [35-37]. ILs can also be used to synthesize active pharmaceutical ingredients (APIs) with modified solubility, increased thermal stability, and a significant enhancement in the efficacy of topical analgesia compared to then-starting materials [38-40]. Furthermore, many ILs exhibit antimicrobial activity [41], which can make them useful as APIs or formulation preservatives and also provide unique opportunities for oral [42] and topical drug delivery [43]. 

---