Introduction

When medications that may require storage over a length of time in liquid form and are unstable, they are often shipped to the pharmacy in powder or crystalline (lyophilized) form requiring reconstitution before administration. Medications such as pediatric antibiotics, injectable antibiotics, or immunization agents are some of the most frequently found medicines in this form. These drugs must have liquid added before their use—liquids in the form of water when the medications are for oral use or in the form of sterile solutions such as sterile water for injection, saline for injection, or diluents supplied by the manufacturer when the medicine is used for parenteral administration. Dissolving the powdered medication in the liquid is called reconstitution.

The dry drug form may be found in single-dose or multidose containers for oral or injectable use. The label on the medication will tell the type of diluent to be used and the amount of the diluent for the desired dosage strength or, in some cases, concentration. The directions on the side of the label should be read carefully to prevent errors in the reconstitution process.

Reconstitution of Powders into Liquid Medications

Medications that are unstable in liquid form for extended periods of time are manufactured in either a powder or crystalline (lyophilized) form for reconstitution before use. To reconstitute a medication, care must be taken to follow the instructions on medication label exactly. Before using the medication, care must be taken that the dry ingredients are completely dissolved or suspended into liquid form by adding a diluent.

When used as an injectable medication, single-dose vials/ampules or multidose vials are available. Available multidose containers are used when a number of doses may be used from the same container within the amount of time that is with the safe time limit after reconstitution. The diluent used for reconstitution for injectable medications must be sterile and may come in a single-dose vial, as for reconstitution of immunizations that are single doses, or in multidose vials such as sterile water for injection used for multiple doses of antibiotics. To reconstitute injectable medications, sterile syringes are used in the appropriate size for the amount of diluent necessary for the manufacturer’s label.

Most oral preparations are found in bottles that are larger than the medication volume present. This allows space for shaking medications before administration. Because the usual vehicle for reconstitution of oral medications is distilled water, graduates are used to measure the quantity of liquid to be added (Figure 9-1). In some pharmacies, a computerized dispenser for distilled water, such as a Fillmaster electronic pharmaceutical water dispenser, is available. When indicating the correct amount of water to be dispensed, this machine provides one half of the necessary diluent, stops and allows time for mixing the powder medication with the diluent, and then dispenses the remainder of the water on demand.

The label on the medication provides the needed information for the necessary volume of diluent to be mixed with the powder to provide the desired dosage per volume. Most oral liquid products are described in dosage strengths that indicate the amount of medication in 1 teaspoonful (5 mL) of medication, whereas the strength described on injectable products varies with the medication and the manufacturer’s instructions based on the intended route of administration. If the medication is a single-strength, single-dose vial, the reconstitution is accomplished by adding the amount of diluent indicated on the label. On the other hand, if the medication vial may be prepared at multiple strengths or concentrations, such as found with antibiotics, the diluent must be adjusted to meet the strength necessary to meet the physician’s order. When reconstituting multiple-strength doses, check the label on the vial for the options available for the route desired and then choose the one closest to that of the physician’s ordered strength for the intended route of administration.

Vials of the same drug may require different volumes and types of diluent for different routes of administration when given parenterally. The directions on the label should be followed exactly to ensure that the correct type and amount of diluent have been used. Some medications may even require specific diluents be added for intramuscular use, such as small amounts of anesthetics to prevent discomfort with administration.

When powders are dissolved in the liquid, the weight or strength of the medication will always remain the same as the amount given on the label. For example, if a label for amoxicillin states that the container holds a total of 2.5 g as a powder, the total weight or strength of the medication will be 2.5 g after reconstitution has occurred. When medications are supplied in dry powder or crystalline form for stability, the space occupied by the powder is known as powder volume or powder displacement. The total liquid volume of the medication will be that of the amount of medication plus the amount of liquid. In the label shown in Figure 9-2, the final volume of the bottle is 100 mL when reconstituted with 78 mL of water (Figure 9-3). So with this reconstitution the powder volume or displacement is 22 mL (100 mL total volume − 78 mL diluent = 22 mL powder volume). Powder volume (Pv) is the difference between the final volume (Fv) and the diluent volume (Dv). This can be shown with the formula Pv = Fv − Dv.

Example 9-1

On the Augmentin label, the instructions state to add 1 teaspoon (approximately 5 mL) of water for a dose of 125 mg/5 mL. On this label, the difference or powder volume would be related to the approximate amount of water added. However, if the label is read as stated, Pv = 5 mL (Fv) − 5 mL (Dv) = 0 (Pv) or Pv = 0. This is not truly correct as the powder volume would be the difference found after adding the 5 mL of water. There is always a powder volume.