The Pharmaceutics and Compounding Laboratory
Pharmaceutical Solutions I:
Simple, Saturated, Syrups

Introduction

The study of pharmaceutical solutions is essential to the practicing pharmacist and can be, at times, somewhat complex. In addition to considering the therapeutic appropriateness of the drug, the pharmacist must consider many factors regarding the chemical and physical aspects of the product. Is the drug soluble in an acceptable solvent? Is it chemically stable in solution and for how long? Are two or more solutes chemically and physically compatible in solution? How will changes in temperature, pH or light exposure affect the product? Should the product be preserved, buffered, or flavored and how? How should the product be packaged and stored?

You may be wondering if you really need to know all of these things when so many products are commercially available. Absolutely! Many oral solutions are not produced commercially because they are unstable and have a short shelf-life or are used in such a small patient population that they are unprofitable to produce commercially. Hence, you may be called upon to formulate and dispense many such products.

As with any product, safety and accuracy of dosing are our ultimate goals. Thus, you must learn to read and interpret the prescription properly, to make the necessary calculations to prepare a product of desired strength, and to use the proper judgments and formulation techniques to ensure a stable, potent product. Finally, you must learn to clearly and accurately label the products with the appropriate instructions for use. There may be times when written or verbal instructions are necessary to supplement the label directions.

A solution is a thermodynamically stable, one-phase system composed of 2 or more components, one of which is completely dissolved in the other. The solution is homogeneous because the solute, or dispersed phase, is dispersed throughout the solvent in molecular or ionic sized particles. Broadly defined, a solution may be any combination of solids, liquids, and/or gases. We will restrict our definition of pharmaceutical solutions to those composed of a solid, liquid, or gas dissolved in a liquid solvent.

The assignment of the terms solute and solvent is sometimes arbitrary. Generally, the solute is the component present in the smallest amount and the solvent is the larger, liquid component. Water is nearly always considered the solvent. Pharmaceutical solutes may include active drug components, flavoring or coloring agents, preservatives, and stabilizers or buffering salts. Water is the most common solvent for pharmaceutical solutions, but ethanol, glycerin, propylene glycol, isopropyl alcohol or other liquids may be used, depending on the product requirements. To be an appropriate solvent, the liquid must completely dissolve the drug and other solid ingredients at the desired concentration, be nontoxic and safe for ingestion or topical application, and be aesthetically acceptable to the patient in terms of appearance, aroma, texture, and/or taste.

The solubility of a drug is the expression of the quantity of a drug that can be maintained in solution in a given solvent at a given temperature and pressure. It is usually expressed as the number of milliliters of solvent required to dissolve 1 gram of the drug. Understanding drug solubility is critical in formulating solutions. This topic will be covered in more depth in a later exercise.

A saturated solution is one that contains the maximum amount of solute that the solvent will accommodate at room temperature and pressure. A supersaturated solution is one that contains a larger amount of solute than the solvent can normally accommodate at that temperature and pressure. It is usually obtained by preparing a saturated solution at a higher temperature, filtering out excess solute and reducing the temperature. Saturated and supersaturated solutions are physically unstable and tend to precipitate the excess solute under less than perfect conditions (e.g. when refrigerated or upon the addition of other additives).

A differentiation is sometimes made between solutions on the basis of solute molecular size. Micromolecular solutions consist of dispersed molecules or ions in the 1-10 A size (MW < 10,000). In macromolecular solutions (MW > 10,0000), the solutes are in true solutions, but the solute size of macromolecular solutions lends special properties to them. Because the particles are so large, most cannot be sterilized by filtration. The solutions are also quite viscous, and may be used as thickening agent for other dispersed dosage forms. Macromolecular solutions include those containing acacia, methylcellulose and other cellulose derivatives, and proteins such as albumin.