Liquid dosage forms formulation additives

A variety of different artificial sweeteners have been approved for use in oral liquid dosage forms by the FDA. One general characteristic for artificial sweeteners is their very high sweetness compare to sucrose. This also results in a much lower concentration needed in the formulation, which can lower the cost and/or risk of incompatibility with the drug or other excipients. Additionally, a sugar-free formulation... 

Stewart and Tucker assert that hydrolysis is affected by pH, buffer salts, ionic strength, solvent, and other additives such as complexing agents, surfactants, and excipients, and each of these factors is discussed in some detail. Waterman et al. (31) provide a comprehensive treatment of hydrolysis as it relates to pharmaceuticals, with thorough discussions of mechanisms, formulation considerations, pH, ionic strength, buffers, solid-state considerations, hydrolysis of lyophiles, liquid dosage forms, packaging, etc. 

Liquids and Suspensions. Most liquid formulations are not packaged in unit-dosage form. Therefore, before administration, the proper amount of medication to be taken for each dose must be measured. This additional requirement may compound any difficulties a patient may have in following a prescribed schedule. Patients suffering from visual impairment, arthritis, or tremors associated with neurological disorders are particularly likely to become frustrated with this type of formulation. Visual impairments make it difficult, if not impossible, for many elderly patients to measure the prescribed amounts of medication accurately. Impaired dexterity, owing to tremors or arthritis, may have effects on a patient s ability to hold both a spoon and a bottle at the same time while pouring out the desired amount of liquid. 

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. 

The liquid formulation for parenteral administration requires additional physical and microbiological functionalities, such as syringeability, sterility, osmolarity, and pyrogen freedom. The particle size change can influence the syringeability of injection of a suspension formulation as well as the level of irritation at the site. Terminal sterilization such as autoclave or gamma irradiation may affect the physical stability of the dosage form. Both formulation and container systems should be evaluated [63]. 

Formulation of liquids usually requires more excipients, in both type and quantity, than for solid dosage forms. They must be carefully selected in paediatric preparations because of possible pharmacological actions or toxic effects. Dose-related adverse effects of excipients are of particular concern in the preterm, low-birthweight neonate and infant due to immaturity of hepatic and renal function in this population. The following is not an exhaustive list but is intended to raise awareness of susceptible excipients to be used in paediatric medication. More emphasis is put on additional agents than on vehicles such as sweeteners and preservatives as they are of particular importance in paediatric liquid formulation and often not extensively taught at undergraduate levels. 

PEG is an amphiphilic polymer that is soluble in both aqueous and organic solvents. In addition it has a low level of cellular and protein absorption and is therefore grafted to surfaces of medical devices to prevent deposition of proteinaceous material or bacterial surface growth. It is also conjugated to proteins and to colloidal dosage forms, e.g., liposomes, to minimise their recognition by the immune system. Furthermore, PEG have been widely reported to increase the solubility of poorly soluble therapeutic agents when formulated as liquid formulations, e.g., oral solutions, injections, and as solid dispersions (a.32). 

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