TThe Pharmaceutics and Compounding Laboratory
Factors Influencing
the Solubility of Drugs

Introduction

One of the primary physicochemical considerations in preparing pharmaceutical solutions is the solubility of the drug in a suitable solvent. Solubility may be defined as the maximum concentration of a substance that may be completely dissolved in a given solvent at a given temperature and pressure. When both solute and solvent are liquids, the term miscibility rather than solubility may be used to describe the affinity between the liquids.

The solubility of a substance may be described in a variety of ways. The USP/NF generally expresses the solubility in terms of the volume of solvent required to dissolve 1 gram of the drug at a specified temperature (eg. 1 g ASA in 300 ml H2O, 5 ml ethanol at 25°C). Other references may use more subjective terms to describe solubility, such as those given in the following table from Remington's.

Descriptive terms Parts of solvent needed for 1 part solute
Very soluble < 1
Freely soluble 1-10
Soluble 10-30
Sparingly soluble 30-100
Slightly soluble 100-1000
Very slightly soluble 1000-10,000
Practically insoluble or insoluble > 10,000

Liquids which form a homogenous system when mixed in any proportion are said to be miscible (eg. water and ethanol). Those in which only certain volume ratios produce homogenous mixtures are said to be miscible in certain proportions (eg. water and chloroform). Immiscible liquids will not produce a homogenous solution in any proportions (eg. water and olive oil).

The aqueous solubility of all drugs is of interest to us, since it is only in the form of an aqueous solution that a drug can be absorbed into the general circulation to exert a therapeutic effect.