INTRODUCTION

Learning Objectives

After completing this chapter, the reader should be able to:

• Define and understand the terms and concepts of solubility and miscibility.

• Identify the descriptive terms for solubility, their meaning, and their percent value.

• Recognize factors that affect solubility.

• Calculate the solubility of poorly soluble strong electrolytes by using Ksp values.

• Calculate the solubility of weak electrolytes as a function of pH and understand what the answer means.

• Calculate the pH of precipitation for weak electrolytes in aqueous and mixed solvent systems.

• Describe the role of drug dissolution from dosage forms in drug bioavailability.

• Relate the parameters of the Noyes–Whitney equation to the variables that affect the dissolution rate of drug particles.

• Recognize and appreciate the United States Pharmacopeia (USP) requirements for dissolution studies.

• Discuss how various physicochemical, formulation, and physiological factors can influence dissolution behavior.

• Define and understand the partitioning law, partition coefficients, and apparent partition coefficients.

• Calculate the partition coefficients for different types of solutes in aqueous/organic solvent systems.

• Determine the effect of pH on the partition coefficient of weak electrolytes and on their excretion in different body fluids.

SOLUBILITY

General Solubility Concepts

Solubility is the concentration of a solute when the solvent has dissolved all the solute that it can at a given temperature. A useful definition of solubility is the concentration of solute in a saturated solution at equilibrium. Saturated solution concentration is the solubility of the solute at that temperature. Solubility is a physical property, and values for the solubility of pure substances are found in the literature. It is possible for some substances to dissolve in a higher concentration than could be attained at equilibrium, have increased solubility, and form supersaturated solutions. One compound that readily forms supersaturated solutions is caffeine. The term miscible is used to refer to the solute when it is a liquid and will form a solution with a solvent over any concentration range.

The solubility of most substances varies with temperature, having a nearly exponential relationship, as seen in one of the solubility curves for two inorganic potassium salts shown in Figure 5-1.

FIGURE 5-1

Solubility curves. Solubility Expressions

The solubility of solid solutes in liquid solvents, particularly in water, is an important consideration in the preparation, storage, and use of liquid pharmaceutical formulations and products.

Descriptive terms for solubility are found in the United States Pharmacopeia/National Formularly (USP/NF) and in Remington's Pharmaceutical Sciences. An interpretation of these terms is given in Table 5-1. The descriptive terms are general solubilities and cover a range of values. For example, a substance described as “soluble” requires between 10 and 30 parts (mL) of solvent to dissolve 1 part (g) of solute.

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