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Excipients in pharmaceutical oral solutions



Excipients in pharmaceutical formulations are physiologically inert compounds that are
included in the formulation to facilitate the administration of the dosage form, e.g. pour-ability, palatability, to protect the formulation from issues regarding physical and chemical stability and to enhance the solubility of the therapeutic agent.


The vehicle

The preferred and most commonly used vehicle in solutions for oral administration is Purified Water USP, due to the low cost and low toxicity of this ingredient. Under normal circumstances tap (drinking) water should not be used due to the possibility of chemical incompatibilities within the formulation. The main features of Purified Water USP are as follows:
·         
     It is prepared by distillation, ion exchange methods or byreverse osmosis.
·        The solid residue (obtained after evaporation) is less than1 mg per 100 ml of evaporated sample.
·      
          It must not be used for the preparation of parenteralformulations.



Co-solvents

As defined previously, co-solvents are employed to increase the solubility of the therapeutic agent within the formulation. Few co-solvents of pharmaceutical importance are explained below

Glycerol

Glycerol (also termed glycerin) is an odorless, sweet liquid that is miscible with water and whose co-solvency properties are due to the presence of three hydroxyl groups (termed a triol). It has similar co solvency properties to ethanol.

Alcohol USP (CH3CH2OH)

Excipients in pharmaceutical formulations are physiologically inert compoundsAlcohol USP contains between 94.9 and 96.0% v/v ethyl alcohol (ethanol) and is commonly used as a co-solvent, both as a single co-solvent and with other co-solvents, e.g. glycerol. The known pharmacological and toxicological effects of this co-solvent have compromised the use of alcohol in pharmaceutical preparations. As a result there are both labelling requirements for preparations that contain alcohol and upper limits with respect to the concentration of alcohol that may be used in formulations.

Propylene Glycol USP

Propylene Glycol USP is an odourless, colourless, viscous liquid diol that contains two hydroxyl groups. It is used in pharmaceutical preparations as a co-solvent, generally as a replacement for glycerin.

Poly (ethylene glycol) (PEG)

PEG is a polymer composed of repeating units of the monomer ethylene oxide (in parenthesis). The physical state of the polymer is dependent on the number of repeat units (n) and hence on the molecular weight. Lower-molecular-weight grades (PEG 200, PEG 400) are preferred as co-solvents in pharmaceutical solutions.

Surface-active agents

Surface-active agents are chemicals that possess both hydrophilic (water-liking) and hydrophobic (water-disliking) regions. At dilute concentrations surface-active agents will orient at the interface between two phases (e.g. water/oil, water/air), with the hydrophilic and hydrophobic regions of the molecule being positioned to the hydrophilic and hydrophobic phases, respectively.

Buffers

Buffers are employed within pharmaceutical solutions to control the pH of the formulated product and, in so doing, optimize the physico-chemical performance of the product. Typically pH control is performed:
·        To maintain the solubility of the therapeutic agent in the formulated product. The solubility of the vast number of currently available drugs is pH-dependent and, therefore, the solubility of the therapeutic agent in the formulation may be compromised by small changes in pH
·        To enhance the stability of products in which the chemical stability of the active agent is pH-dependent.

Sweetening agents

Sweetening agents are employed in liquid formulations designed for oral administration specifically to increase the palatability of the therapeutic agent. The main sweetening agents employed in oral preparations are sucrose, liquid glucose, glycerol, sorbitol, saccharin sodium and aspartame.

Viscosity-enhancing agents

The administration of oral solutions to patients is usually performed using a syringe, a small-metered cup or a traditional 5-ml spoon. The viscosity of the formulation must be sufficiently controlled in order to ensure the accurate measurement of thevolume to be dispensed. Furthermore, increasing the viscosity of some formulations may increase the palatability. Accordingly there is a viscosity range that the formulation should exhibit to facilitate this operation. Certain liquid formulations do not require the specific addition of viscosity-enhancing agents, e.g. syrups, due to their inherent viscosity.

Antioxidants

Antioxidants are included in pharmaceutical solutions to enhance the stability of therapeutic agents that are susceptible to chemical degradation by oxidation. Typically antioxidants are molecules that are redox systems which exhibit higher oxidative potential than the therapeutic agent or, alternatively, are compounds that inhibit free radical-induced drug decomposition.



Preservatives

Preservatives are included in pharmaceutical solutions to control the microbial bioburden of the formulation. Ideally, preservatives should exhibit the following properties:
·        possess a broad spectrum of antimicrobial activity encompassing Gram-positive and Gram-negative bacteria and fungi
·        be chemically and physically stable over the shelf-life of the product
·        Have low toxicity.

Flavours and colourants

Unfortunately the vast majority of drugs in solution are unpalatable and, therefore, the addition of flavours is often required to mask the taste of the drug substance. Taste-masking using flavours is a difficult task; however, there are some empirical approaches that may be taken to produce a palatable formulation.


Excipients in pharmaceutical oral solutions Excipients in pharmaceutical oral solutions Reviewed by gafacom on October 01, 2019 Rating: 5

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