Reconstitution of Powders or Crystals into Liquid Medications

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Chapter 9

Reconstitution of Powders or Crystals into Liquid Medications

Objectives

• Read labels of powders or crystals (lyophilized) medications to determine correct diluent and correct volume necessary to reconstitute powders

• Check labels for expiration dates and storage conditions before and after reconstitution of solid medication to a liquid form

• Understand the importance of labeling reconstituted medications with date, time, and initials of person performing the medication reconstitution

• Determine the appropriate amount of diluent necessary when using a single-dose container of a powder or crystals

• Determine the appropriate amount of diluent necessary when preparing a multidose container of a powder or crystals

• Determine the appropriate dilution concentration when more than one dosage strength in the multidose container is possible, and then determine amount of diluent necessary to meet desired concentration

• Calculate the amount of medication of a reconstituted medication to be dispensed to meet the physician’s order

Key Words

Pretest

Complete the following reconstitution of the medications to supply the dosage necessary for a physician’s order. Show your calculations. Be sure all calculations are made to a measurable amount.

image 1 A physician orders penicillin G 200,000 units to be given IM q12h × 5 d for a child. As the pharmacy technician in the hospital pharmacy, you are to prepare the powdered medication for administration by injection. It is desirable for the intramuscular (IM) injection dose not to exceed 1 mL in volume for this child. You have the label for a multidose vial from which to prepare the medication. Determine the correct reconstituted concentration for use with this patient.

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image 2 A physician orders penicillin G 250,000 units q6h IM. The medication is available in a 1,000,000-unit multidose vial. The label reads to reconstitute the medication with either sterile water for injection or isotonic sodium chloride for injection using the following instructions:

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image 3 A physician orders Mefoxin 1.2 g IM q8h. The medication available is a 2-g vial for reconstitution. The label reads as follows:

MEFOXIN CONCENTRATION AMOUNT OF DILUENT TO BE ADDED AMOUNT THAT CAN BE DRAWN
400 mg/mL 4 mL for IM use 5 mL
180 mg/mL 10 mL for IV use 10.5 mL

image 4 A physician orders ampicillin 500 mg IM q6h. The available medication is a 1-g vial. The following label is on the vial:

AMPICILLIN CONCENTRATION AMOUNT OF DILUENT
250 mg/mL 3.4 mL

image 5 A bottle of ampicillin is marked 125 mg/5 mL for a child. The 200-mL bottle instructs that 158 mL of water be added for an oral suspension. The physician wants the child to receive ampicillin 250 mg qid.

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What is the total strength of medication in milligrams in the bottle? __________

Hint: Use ratio and proportion to complete this answer.

What volume of water is added for the bottle to have the correct concentration? _________ Show on the graduates the volume of water needed for reconstitution.

What is the volume per dose that the child should receive? ____________________

What dose volume would you tell the parent to give in household measurements? ____________________

Is the volume in the one container sufficient for 10 days? __________ Show your work. Explain your answer. ____________________

If necessary, how many mL of medication are needed to complete the prescription as designated? ____________________

What is the total volume of liquid in milliliters in the container after reconstitution? ____________________

What is the powder volume of this medication? ____________________

image 6 A bottle of Veetids after reconstitution will contain 125 mg/5 mL. The bottle states that the total volume in the bottle will be 100 mL after reconstitution.

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image 7 A label for ticarcillin for injection for IV and IM use shows that the vial contains 1 g of medication in 2.6 mL of reconstituted medication for IM use. The instructions state to use at least 4 mL of sterile water for injection for IV use. To prepare an IM solution, add 2 mL of sterile diluent. Use the solution promptly after reconstitution.

What is the dosage strength found in this vial once prepared for IM use? ____________________

What is the diluent volume for IM use? ____________________

If 5 mL of sterile water has been added to the medication for IV use, what volume of medication would be added to the IV fluids to provide the medication for an order of 750 mg? Base your answer on the fact that the entire vial will contain 6 mL of medication. ____________________

What volume of medication is prepared for injection if the physician orders 500 mg IM stat? ____________________

The physician then orders 250 mg IM every 8 hours. What volume of medication would be given with each dose? ____________________

Can the remainder of the vial be used for the subsequent injections? ____________________ Explain your answer. ____________________

image 8 A vial of Solu-Medrol is being reconstituted for a patient with severe allergies. The label reads to reconstitute the medication with 8 mL of bacteriostatic water for injection with benzyl alcohol. When reconstituted, each 8 mL will contain 500 mg. The solution will remain stable between 15° and 30° C for 48 hours after mixing.

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What is the total strength of medication in a vial? ____________________

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    What is the total strength of medication in the container in grams? __________

What is the diluent volume that should be added to the medication when reconstituting to the strength designated on the container? ____________________

Show on the graduates the water volume to be added to the solid medication.

What is the dose strength of the medication following reconstitution? __________

How long is the medication stable after reconstitution, when stored as indicated? ____________________

What storage information needs to be supplied to the patient when this medication is dispensed? ____________________

What volume of medication is necessary to give a child a dose of 400 mg? ____________________

What would you tell the parent to give the child a dose in household measurements? ____________________

What volume of medication, in the household measurement system, should be given for an order of 500 mg? ____________________

What is the powder volume in the bottle? ____________________

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.

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FIGURE 9-1 Examples of graduated cylinders.

Tech Note

Flavorings are available to add to reconstituted medications to make them more palatable.

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.

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FIGURE 9-2 This label for Amoxil specifies that the total liquid volume of the medication will be 100 mL when reconstituted with 78 mL of water.
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FIGURE 9-3 Graduated cylinder shows amount of water necessary (78 mL) for the reconstitution of the powder in Figure 9-2.

Example 9-1

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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.

Tech Note

Be sure to calculate the total volume in container prior to calculating “Pv.”

Example 9-2

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In this example, the bottle of erythromycin will contain 200 mL total (or final) volume with a dose strength of 250 mg/mL after reconstruction with 140 mL of distilled water (Dv).

< ?xml:namespace prefix = "mml" />Pv=200mL(Fv)−140mL(Dv)

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Pv=60mL

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Example 9-3

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The label for Zithromax for injection shows a reconstituted strength of 100 mg/mL. The total dosage in the vial is 500 mg. Therefore the vial contains 5 mL after reconstitution. The directions for reconstitution state to add 4.8 mL of sterile water for injection.

Pv=5mL(Fv)−4.8mL(Dv)

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Pv=0.2mL

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The total weight of the drug, as well as the total volume, are important when preparing the medication for dispensing when reconstitution is needed. The amount dispensed must be adequate to provide the dosage prescribed by the physician and must be in a volume appropriate for the ordered route of administration and the characteristics of the patient for whom the drug was ordered. The manufacturer determines the amount of diluent that should be added to each drug powder in the specific container for the desired dose. With oral medications, the container is usually sufficient for the usual volume of medication for the usual length of time the medication is prescribed, such as 10 to 14 days for antibiotics. However, in some instances, such as unavailability of drug in the needed dosage for the physician’s order, it is not uncommon to partially fill a prescription with a smaller container and provide the remainder when the pharmacy obtains the balance of the needed supply. In other situations, a drug normally intended for pediatric use will be needed to provide adult dosing, and more than one bottle of the selected medication liquid may be needed to fill an entire adult prescription for the desired length of time.

Tech Note

Be aware that medications for intramuscular (IM) and intravenous (IV) use are not interchangeable. The label on the medication will give its exact use. Some medications will indicate that IM or IV use is acceptable but will usually show a difference in the amount of diluent to be added. Many medications for IV use may not be given directly from the vial, but require even further dilution in intravenous fluid prior to administration. Some medications are manufactured to be used for only one route of administration. As a pharmacy technician, you must read the product label closely to be sure the correct route as well as the correct medication and its concentration has been selected for the amount prescribed before reconstitution. Remember that after reconstitution, many of the medications have short expiration dates—some products even expire in hours, not days.

Practice Problems A

Calculate the powder volume using each of the labels that follow.

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    What is the powder volume for this medication? ____________________

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    What is the powder volume for this medication given intramuscularly? ____________________

3. image

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What is the powder volume for intramuscular use? ____________________

4. image

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    What is the powder volume of this medication? ____________________

5. image

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What is the powder volume for this medication? ____________________

Basic Principles of Reconstitution

Think of reconstitution as a means of mixing a powdered form of chocolate flavoring into a glass of milk. You have the powder and you add the milk (or the diluent) a little at a time to prevent the powder from clumping as the liquid is added. The same steps are used with the reconstitution of medication powders.

image Tech Alert

Always remember to tap the vial or the bottle of medication to be reconstituted to loosen any medication that may be attached to the side of the container.

The most important step in reconstituting the powder is to read the label or package insert directions carefully because these provide the road map for correct reconstitution. The label tells you the total quantity of the drug in the container, the volume and type of diluent (usually in milliliters) to use for reconstitution, and the final strength (weight) or concentration of the medication following the reconstitution process. The information also includes the length of time the medication is stable and the storage needs following reconstitution. These directions must be read carefully and followed exactly each time a medication is reconstituted.

image Tech Alert

Never assume the directions are the same as previously found on the same medication—READ the label directions every time medication is reconstituted.

Tech Note

The usual diluent for mixing a powder for an oral medication is either distilled water or, if different, as indicated by the manufacturer. The diluent with injectable medications may vary with each drug. Some injectable powders come with the diluent in two separate chambers, one for the powder and another for the diluent as with Solu-Medrol (methylprednisolone sodium succinate) or hydrocortisone sodium succinate (Figure 9-4). This system is called the Act-O-Vial system. In this case when the plunger is dislodged by pushing, the diluent drops from the upper chamber into the lower chamber which contains the powder. In other cases when a special diluent is necessary, this diluent may be packaged separately and supplied with the medication such as with some immunization agents. In these cases, finding the designated diluent is not necessary, because the manufacturer has included it.

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FIGURE 9-4 An Act-O-Vial.

In cases where the diluent is not supplied, reconstitution of the powder will use a diluent required by the manufacturer. With injectable medications the manufacturer may choose to use either sterile water for injection or sterile normal saline. Some drugs may use bacteriostatic water for injection when used for IM injections. Some parenteral medications may even require the use of dextrose 5% in water for reconstitution. If the solution for reconstitution is not indicated, most medications can be mixed safely with sterile water. If the directions for reconstituting the medicine are not available, consult a drug reference.

Once the label has been read and the diluent of choice is known, the amount of diluent for the desired dosage must be verified. In single-dose vials, the amount of diluent will be one volume because a single dose will be given. In multidose vials, multiple instructions for different strengths following reconstitution may be possible and will be indicated on the label, each showing the amounts necessary for reconstituting to a particular strength (Figure 9-5). Read the possible concentrations or strengths following reconstitution, because typically the desired strength per volume should be the closest to the amount of the order and should also match the intended route of administration. Decide on the amount of diluent that will be added and prepare this for use. Remember that when adding diluent, the less fluid added to a specific container of medication, the more concentrated the medication—or “less is more” (Figure 9-6).

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FIGURE 9-5 Label showing the volume of diluent necessary for reconstituting to a particular strength when multiple dosages are a possibility.
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FIGURE 9-6 Diluting oxacillin sodium in sterile water for injection.

Tech Note

When reconstituting medications with multiple strengths possible, choose the strength closest to the physician’s order or the strength that will provide a dose with the least chance for error.

After injecting diluent, the mixing process for an injectable medication should be accomplished by inverting the container slowly, unless otherwise specifically indicated by the manufacturer. Shaking the container may decrease the effectiveness of the medication and may also cause the liquid to foam. Foaming will prevent the correct amount of medication from being withdrawn for injection and may even prevent the medication from being drawn from the vial.

Be sure you know the length of time that the medication is stable and the directions for storage for both before and after the reconstitution. After the powder has been mixed, the person who did the reconstitution should add the following to the label if the container holds more than one dose and not all of the medication is used at time of reconstitution:

Remember that the final volume of medication in the container will always be greater than the amount of diluent added because of powder volume. Thus the total volume prepared should always be checked to ensure there is an adequate amount for dispensing of the prescription or order; if not, be sure the correct medication strength has been chosen and reconstituted as required to meet the order. Usually the medication label also gives the total volume of medication after mixing according to indicated directions (e.g., see Figure 9-2, in which the label for Amoxil indicates the total amount of reconstituted medication is 100 mL).

Tech Note

Patient safety is of utmost importance and should be safeguarded throughout each step of handling medications, especially medications requiring reconstitution.

Practice Problems B

Answer the following questions and make necessary calculations as indicated.

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    What is the total dosage of medication found in this container? ____________________

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What is the total dosage of medication in this vial? __________

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What is the total volume of medication after reconstitution? __________

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What two drugs are in this medication? __________

What diluent volume should be added? __________

On the graduate, show the volume of diluent to be added.

What special directions are necessary when adding the diluent? __________

On the label, what is the first direction necessary for reconstitution? __________

What is the total volume of medication available after reconstitution? __________

What is the volume of medication necessary for a dose of 250 mg? __________

What is the volume of a dose of medication given in household measurements? __________

What instructions are given to the patient when dispensing? __________

What are the storage requirements prior to reconstitution? __________

What are the storage requirements after reconstitution? __________

How long is the reconstituted medication stable? __________

How many doses are available in this container if the child for whom it is prescribed receives 125 mg tid? __________

What is the powder volume? __________

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The instructions state 1.6 mL of diluent is used for IM use (1 gm = 2 mL).

6. image Order: Ampicillin 250 mg IM tid

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What is the total medication dosage found in the container? __________

If 75 mL of diluent is added to the container, what is the dosage per mL? __________

If 11.5 mL of diluent is added to the container, what is the dosage per mL? __________

What is the route of administration for this medication? __________

What diluent is used to reconstitute this medication? __________

How long is the medication stable in the refrigerator after reconstitution? __________

If the medication is reconstituted to 250,000 units/mL, how many milliliters would be necessary for 375,000 units? __________

If reconstituted to 1,000,000 units/mL, how many milliliters would be necessary for 2,500,000 units? __________

What is the powder volume for 1,000,000 units/mL? ____________________

What is the powder volume for 250,000 units/mL? ____________________

What is the powder volume for 500,000 units/mL? ____________________

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What is the total medication dosage in this vial? __________

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    What is the total medication dosage in the vial? __________

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    What is the total medication dosage in the bottle? ____________________

What diluent is used for reconstitution? ____________________

What diluent volume is added for reconstitution? ____________________

Show the amount of diluent on the graduate provided.

What special directions are necessary for reconstitution? ____________________

What is the medication strength after reconstitution? ____________________

Why is the container oversized? ____________________

What storage directions must be given to the patient? ____________________

How long can the medication be kept without loss of potency? ____________________

What is the total volume in the bottle after reconstitution? ____________________

What metric dose of medication would be in a teaspoonful? ____________________

How many total milliliters would be necessary for 375 mg/d? ____________________

How long would this container of medication last when given to the previous order? ____________________

How long would the container of medication last if 250 mg bid were the order? ____________________

What is the powder volume? ____________________

Review

Reconstitution is necessary when a medication is unstable for storage in a liquid form. Most medications that need reconstitution come in powders, but some are in a crystalline form. When the medication will be used for injectable routes, the diluent may be sterile water for injection, bacteriostatic water for injection, 0.9% sodium chloride (normal saline) injectable, or a special solution provided with the medication by the manufacturer. If the medication is for oral use, distilled water is the common vehicle for reconstitution. After reconstitution, these medications require special storage because of the instability of the liquid medication. Some medications can be diluted to different strengths or concentrations as directed by the manufactures, whereas others have only one-strength dilution. Some drugs are found in single-dose vials for reconstitution, and others are found in multidose vials. Because of the variances in the reconstitution of these medications, their labels must be read closely by the pharmacy technician with each reconstitution so he or she can choose the correct diluent and the amount that will provide the nearest dosage to the physician’s order for the route of administration. Always read labels of drugs for reconstitution; never assume that the label will be the same for the amount of diluent as previously prepared, because changes to product formulations may result in new directions for reconstitution.

Several steps are necessary in preparing reconstituted medications:

1. Read all of the directions on the medication label before starting the procedure.

2. Tap the bottle to loosen the powder in the bottle or vial.

3. Use the diluent that is designated by the manufacturer in the amount that is appropriate for the concentration or strength of medication necessary for the physician’s order. If this information is not on the vial or bottle, use a drug reference for the appropriate diluent and amount.

4. After reconstitution of injectable label the medication with the initials of the person who reconstituted the medication, the date and time of reconstitution, the strength of the medication, and the expiration date and time for oral medications, be sure the time of expiration is excluded on the container label.

5. Remember that the final volume of the reconstituted powder will always be greater than the amount of diluent added because of the powder volume (Pv = Fv − Dv).

Posttest

Before taking the Posttest, retake the Pretest to check your understanding of the materials presented in this chapter. All dose measurements should be in a measurable volume, especially with injectable medications.

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What is the total dosage of medication in the container? __________

What is used as the diluent for reconstitution? __________

What volume of diluent is added? __________ Show the volume of diluent on the graduate.

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What is the medication concentration after reconstitution? __________

What volume of medication is necessary in the metric system to give 400 mg? __________

What volume would 200 mg be in household measurements? __________

What are the storage requirements before reconstitution? __________

What are the storage requirements after reconstitution? __________

How long is the medication potent after reconstitution? __________

What is the total volume in the container after reconstitution? __________

What is the route of administration of the medication? __________

How many total doses are in the container if 400 mg is given bid? __________

What is the powder volume? ____________________

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What is the total strength of medication in the vial? __________

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What is the total strength of medication in the vial? __________

image 4 The physician orders Lorabid 200 mg po for a dose.

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If a physician orders Ceclor 62.5 mg po for a child, what is the dose volume? __________

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What is the total dosage in this vial? ____________________

image 7 A physician orders Mandol 500 mg to be given qid in equal doses.

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image 8 A physician orders potassium phosphate 7.5 mM IV in 100 mL D-5-NS to be given today in previously ordered IV fluids.

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image 9 A physician orders Tagamet 150 mg IV in D-5-W 100 mL q6h.

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What is the strength of this medication following reconstitution? __________

What diluent should be used for this medication? __________

What total volume of diluent should be added to the medication for reconstitution? __________

Show the volume of diluent on the appropriate graduate.

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What volume of diluent should be used with the first addition for reconstitution? ____________________

If the physician orders Amoxil 500 mg tid for an adult, how many milliliters of medication are administered with each dose?____________________

If the medication dose is given tid, how many days would this bottle of medication last? ____________________

How many containers of medication are necessary to fill an order for a 10-day supply? ____________________

What are the storage requirements for the medication after reconstitution? ____________________

What is the powder volume? ____________________

Review of Rules

Reconstitution of Powdered Medications

• Before reconstituting any powdered medication for dispensing, carefully read all directions on the medication.

• Use the exact diluent designated by the manufacturer in the amount that is appropriate for the desired concentration or strength of medication. If this information is not available on the label, use a drug reference for the appropriate diluent and amount. Be sure that the diluent does not have an expiration date that falls before its use date.

• After reconstitution, label the medication with the initials of the person who did the reconstitution, the strength of the medication as reconstituted, and the expiration date and time for parenteral medications. For reconstituted oral medications, the length of time before expiration or the date of expiration should be noted.

• Remember that the volume of medication after reconstitution will always be greater than the diluent added because of powder volume.

• Powder volume may be calculated by subtracting diluent volume from the total or final volume (Pv = Fv − Dv).

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