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.