The Pharmaceutics and Compounding Laboratory
Pharmaceutical Solutions II:
Nonaqueous Solutions

Introduction

Although from their physical properties many solvents appear to be desirable for use in pharmaceutical products, the physiological actions of the solvents greatly limit their use. With few exceptions, most organic solvents are irritating or toxic.

Aromatic hydrocarbons cause paralysis of the central nervous system and are irritating to the skin; methyl alcohol is toxic, and butyl and amyl alcohol are irritating; volatile ethers paralyze the central nervous system, and are irritating to mucous membrane increases; ketones are mildly irritating; and the low molecular weight esters are irritating. Thus, toxicity and irritation limit the solvents employed to a few compounds such as glycerin, alcohol, and propylene glycol for internal use. For external use saturated aliphatic hydrocarbons, ether, and glyceryl esters of aliphatic acids may be added to the list of acceptable pharmaceutical solvents.

Propylene glycol has been employed as a solvent for oral and parenteral solutions of drugs such as antihistamines, barbiturates and vitamins. Although orally administered propylene glycol has a low toxicity in animals, it may exhibit a weak central nervous system depressant activity and an antagonistic action against pentylenetetrazol. Thus, the use of propylene glycol as a physiologically inert solvent is not recommended. Infants with rickets have become stuporous for hours after treatment with 600,000 units of vitamin D administered in 60 ml of propylene glycol as single or divided doses in a 24-hour period.

Nonaqueous solutions are those solutions which contain solvents other than water, either alone or in addition to water. Alcohol or a binary mixture containing alcohol is the most commonly used nonaqueous solvent. In addition to the pharmaceutical classes of elixirs, spirits, tinctures, and fluid-extracts, individual products such as Chloroform Liniment and Coal Tar Solution are alcoholic solutions.