5.2 Active Versus Inactive Drug Ingredients

Oral drug compounds contain one or more active ingredients along with inert, or inactive, ingredients. There are many reasons for the addition of inert ingredients. They fulfill functions of the compound that are not directly related to the medicinal purpose.

For example, one inert ingredient may be a diluent, a filler substance that creates a usable size of tablet or liquid from a small amount of a high-potency active ingredient. Other purposes for inert ingredients may be to bind the compound together, stabilize the ingredients, preserve them, put them in a solution, or give the tablet an appealing color. Common types of inert ingredients used in tablets and their functions are listed in Table 5.2. Patients may be allergic to inert ingredients. All inert ingredients must be listed in the manufacturer product insert that accompanies the prescription product. For over-the-counter (OTC) products, the inert ingredients must be listed for the consumer on the product labeling.

The active drug ingredients in many tablets, capsules, and suspensions are often powders or granules (small particles). At times the active ingredient can be combined with a mineral to form a tightly bonded crystal granule form, or ionized salt, to extend the shelf life of the drug or affect the characteristics of how the drug is released into the bloodstream. Different salt forms are not the same and cannot be substituted without physician direction or approval. For example, diclofenac tablets exist in two salt forms: diclofenac potassium and diclofenac sodium. They have different chemical makeup and crystalline sizes. At equivalent doses, their therapeutic effect would be similar but not the same, and neither the pharmacy technician nor the pharmacist can substitute one for the other without contacting the prescriber.

Drug compounds can be formulated to have the active ingredients directly released or to have delayed-release characteristics to allow for less frequent dosing and/or fewer side effects. The different ingredients and salt or non-salt forms help determine this. Also, the same chemical salt can have different crystalline sizes, which influences how fast the active drug ingredients are released. For example, a Macrodantin 100 mg capsule contains 75 mg of mononitrate salt and 25 mg of a controlled-release macrocrystalline (large crystal) mononitrate salt. This formulation offers better absorption (particularly when taken with food), less nausea and GI upset, and a longer duration of action when compared with a generic drug that contains only 100 mg of the mononitrate salt.

Some drugs have salts for different dosage forms. For example, hydroxyzine 50 mg is available as a hydrochloride salt tablet formulation and as a pamoate salt capsule. In this case, the two different dosage forms are considered therapeutically equivalent. Therefore, if the pharmacy is out of stock of one dosage form, the other dosage form could be safely substituted—but only with the approval of the pharmacist and/or prescriber.

However, this substitution process for dosage form (e.g., capsule versus tablet) is not always possible. For example, Zanaflex 4 mg capsules and Zanaflex 4 mg tablets are not considered therapeutically equivalent and, consequently, cannot be substituted. In many cases, prescribers may not be familiar with which dosage forms are available or the subtle differences in bioavailability or release characteristics among drug products. Pharmacist review of the medication substitution, therefore, is critical.