1. Selected Calculations in Contemporary Compounding
University of Sulaimani Faculty of Medical Science/ School of Pharmacy 2nd Stage Pharmaceutical Orientation
Selected Calculations in Contemporary Compounding
Lecture (5)
Shahen S. Mohammed
MSc pharmaceutics

2. Pharmaceutical compounding vs pharmaceutical manufacturing
Pharmaceutical compounding is the process by which pharmacists combine therapeutically active ingredients with pharmaceutical materials in the preparation of prescriptions and medication orders to meet the specific needs of individual patients.

3. This is in contrast to the large-scale production of pharmaceutical products to meet the needs of the general population that is termed pharmaceutical manufacturing.

4. General Considerations in Compounding Practice
• the need to adjust the strength or dose of a commercially available product to meet the specific requirements of a patient (e.g., a pediatric patient); • the need to provide a product more organoleptically acceptable (e.g., taste) to a pediatric; • the need to prepare a different dosage form (e.g., a liquid) than the commercially available product (e.g., a tablet) to meet the requirements of a patient unable to swallow the existing dosage form (e.g., a pediatric or elderly patient);

5. Constitution of Dry Powders
Constitution of Dry Powders for Oral Solution or Suspension
Some drugs, most notably antibiotics,
lose their potency in a relatively short
period when prepared in a liquid dosage form.
To enhance the shelf-life of these drugs,
manufacturers provide products to the
pharmacy in dry powder form for constitution
with purified water or special diluent at the
time a prescription or medication order is
received.

6. Depending on the product, the dry powder may be stable for about 24 months. After constitution, the resultant solution or suspension is stable in the quantities usually dispensed, for up to 10 days at room temperature or 14 days if maintained under refrigeration.

7. Dry powders for constitution are packaged in
self-contained bottles of sufficient size to
accommodate the addition of the required
volume of diluent.
In addition to the quantitative
amount of therapeutic agent, the powder
contains such pharmaceutical ingredients
as solubilizing or suspending agents, stabilizers,
colorants, sweeteners, and flavorants.

8. Depending on the product’s formulation, constitution results in the preparation of a clear solution (often called a syrup) or a suspension. The final volume of product is the sum of the volume of solvent or diluent added and the volume occupied by the dissolved or suspended powder mixture.
These products generally are intended for infants and children but also can be used by adults who have difficulty swallowing the counterpart solid dosage form products, such as tablets and capsules.

9. Example Calculations for the Constitution of Dry Powders for Oral Use
The label for a dry powder package of cefprozil (CEFZIL) for oral suspension directs the pharmacist to add 72 mL of purified water to prepare 100 mL of suspension. If the package contains 2.5 g of cefprozil, how many milligrams of the drug would be contained in each teaspoonful dose of the constituted suspension?

11. Label instructions for an ampicillin product call for the addition of 78 mL of water to make 100 mL of constituted suspension such that each 5 mL contains 125 mg of ampicillin. Calculate the volume of dry powder in the product and the total content of ampicillin.
Volume of dry powder: Because the addition of 78 mL of water results in the preparation of 100 mL of product, the volume occupied by the dry powder is:
100 mL - 78 mL = 22 mL

12. Total drug (ampicillin) present: If, in the constituted product, each 5 mL contains 125 mg of ampicillin, the total amount of ampicillin in the 100-mL product is:

13. Using the product in the previous example, if a physician desires an ampicillin concentration of 100 mg/5 mL (rather than 125 mg/5 mL), how many milliliters of water should be added to the dry powder?
Because it was determined that 2500 mg of ampicillin are in the dry product, the volume of product that can be made with a concentration of 100 mg/5 mL may be calculated by:

14. Then, because it had been determined that the dry powder occupies 22 mL of volume, it is possible to determine the amount of water to add:
125 mL - 22 mL = 103 mL

15. Constituion of Dry Powders for Parenteral Solution
Because of instability in liquid form,
some medications (particularly antibiotics)
intended for injection are provided as dry
powder in vials to be constituted with sterile
water for injection or other designated
solvent or diluent immediately before use.
Generally, these medications are
small-volume products intended for
use by injection or as additives to
large-volume parenterals.

16. In contrast to the dry powders intended for oral use after constitution, injectable products may contain only limited amounts of specified added ingredients to increase the stability and effectiveness of the drug (obviously, no colorants, flavorants, or sweeteners are added). So, in effect, the bulk volume of the dry contents of a vial is largely or entirely the medication.

17. If the quantity of the dry drug powder is small and does not contribute significantly to the final volume of the constituted solution, the volume of solvent used will approximate the final volume of solution. For example, if 1000 units of a certain antibiotic in dry form are to be dissolved, and if the powder does not account for any significant portion of the final volume, the addition of 5 mL of solvent will produce a solution containing 200 units/mL.

18. If the dry powder, however, because of its bulk, contributes to the final volume of the constituted solution, the increase in volume produced by the drug must be considered, and this factor must then be used in calculating the amount of solvent needed to prepare a solution of a desired concentration. For example, the package directions for making injectable solutions of piperacillin sodium specify that 4 mL of sterile solvent should be added to 2 g of the dry powder to produce 5 mL of a solution that is to contain 400 mg/mL. The drug, in this case, accounts for 1 mL of the final volume.
Again, in dissolving 20,000,000 units of penicillin G potassium, the addition of 32 mL of sterile solvent provides a total volume of 40 mL of a solution that contains 500,000 units/mL. The dry powder now accounts for 8 mL of the final volume.

19. Example Calculations for the Constitution of Dry Powders for Parenteral Use
Using a vial containing 200,000 units of penicillin G potassium, how many milliliters of solvent should be added to the dry powder in preparing a solution having a concentration of 25,000 units/mL?

20. Using a vial containing 200,000 units of penicillin G sodium and sodium chloride injection as the solvent, explain how you would obtain the penicillin G sodium needed in preparing the following prescription.
R Penicillin G Sodium ,000 units per mL
Sodium Chloride Injection ad 10
Sig. For IM Injection mL
15,000 units × 10 = 150,000 units of penicillin G sodium needed

21. Because the dry powder represents 200,000 units of penicillin G sodium or 4⁄3 times the number of units desired, 3⁄4 of the powder will contain the required number of units.
Step 1. Dissolve the dry powder in 4 mL of sodium chloride injection.
Step 2. Use 3 mL of the constituted solution.
Step 3. complete the volume to 10 ml by sodium chloride injection.

22. The package information enclosed with a vial containing 5,000,000 units of penicillin G potassium (buffered) specifies that when 23 mL of a sterile solvent are added to the dry powder, the resulting concentration is 200,000 units/mL. On the basis of this information, how many milliliters of sterile water for injection should be used in preparing the following solution?
R Penicillin G Potassium (buffered) ,000,000 units
Sterile Water for Injection q.s.
Make solution containing 500,000 units per mL
Sig. One mL = 500,000 units of Penicillin G Potassium

23. The package information states that the constituted solution prepared by dissolving 5,000,000 units of the dry powder in 23 mL of sterile solvent has a final volume of 25 mL. The dry powder, then, accounts for 2 mL of this volume.
Step 1. The final volume of the prescription is determined as follows:
Step mL - 2 mL (dry powder accounts for this volume) = 8 mL.

24. Piperacillin Sodium 250 mg Sodium Chloride Injection ad 15 mL
Piperacillin sodium is available in 2-g vials, and the dry powder accounts for 1 mL of the volume of the constituted solution. Using a 2-g vial of piperacillin sodium and sodium chloride injection as the solvent, explain how you could fill the following medication order.
Piperacillin Sodium mg
Sodium Chloride Injection ad 15 mL
Step 1. Dissolve the 2 g of dry powder in 9 mL of sodium chloride injection to prepare 10 mL of solution. Each milliliter will contain 200 mg of piperacillin sodium.
Step 2. Use 1.25 mL of the constituted solution and mL of sodium chloride injection.

25. Use of Prefabricated Dosage Forms in Compounding
Pharmacists frequently find that bulk supplies of certain proprietary drug substances are not available for extemporaneous compounding and that prefabricated tablets, capsules, injections, and other dosage forms provide the only available source of the medicinal agents needed. This situation occurs, for example, when an adult or pediatric patient is unable to swallow solid dosage forms, and the commercially available tablets or capsules must be used to prepare a liquid form of the same medication.

26. When using commercially prepared dosage forms as the source of a medicinal agent, the pharmacist selects products that are of the most simple, economic, and convenient form. For example, uncoated tablets or capsules are preferred over coated tablets or sustained- release dosage forms.
For both convenience and economy, use of the fewest dosage units is preferred; for example, five 100-mg tablets rather than one hundred 5-mg tablets.

27. Occasionally, when of the prescribed strength, small whole tablets may be placed within capsule shells when capsules are prescribed. In most instances, however, tablets are crushed in a mortar and reduced to a powder.
When capsules are used as the drug source, the capsule shells are opened and their powdered contents are expelled. The correct quantity of powder is then used to fill the prescription or medication order.

28. It is important to understand that in addition to the medicinal agent, most solid dosage forms contain additional materials, such as fillers, binders, and disintegrants. These ingredients may need to be considered in the required calculations. For example, a tablet labeled to contain 10 mg of a drug may actually weigh 200 mg or more because of the added ingredients.

29. Example Calculations for the Use of Prefabricated Dosage Forms in Compounding
Only capsules, each containing 25 mg of indomethacin, are available. How many capsules should be used to obtain the amount of indomethacin needed in preparing the following prescription?
R Indomethacin mg/mL
Cherry Syrup ad mL
Sig. 5 mL b.i.d.
Because 2 mg/mL of indomethacin are prescribed, 300 mg are needed in preparing the prescription. Given that each capsule contains 25 mg of indomethacin, then
300 (mg) ÷ 25 (mg) = 12 capsules are needed

30. How many milliliters of an injection containing 40 mg of triamcinolone per milliliter may be used in preparing the following prescription?
R Triamcinolone %
Ointment Base ad 120 g
Sig. Apply to affected area.

31. The only source of potassium permanganate is in the form of tablets for topical solution, each containing 0.3 g. Explain how you would obtain the amount of potassium permanganate needed for the following prescription.
R Potassium Permanganate solution 250 ml
1:5000
Purified water qs
Sig. Use as directed.
1:5000 = 0.02%

32. 250 g × = 0.05 g or 50 mg of potassium permanganate needed Because one tablet for topical solution contains 300 mg of potassium permanganate or 6 times the amount needed, 1⁄6 of the tablet will contain the required amount, or 50 mg. The required quantity of potassium permanganate may be obtained as follows:
Step 1. Dissolve one tablet for topical solution in enough purified water to make 60 mL of dilution.
Step 2. Take 10 mL of the dilution

33. Special Calculations: Capsule Filling
The extemporaneous filling of capsules enables the pharmacist to prepare patient-specific doses of drugs in a conveniently administrated form. Empty capsule shells, made of gelatin, are readily available in a variety of sizes, with size 000 being the largest and size 5 the smallest. Filled capsules should be neither underfilled nor overfilled but should hold the ingredients snugly. Different drug powders have different densities, and thus different weights can be packed into a given size capsule.
In filling a prescription or medication order, a pharmacist should select a capsule size that accommodates the fill and will be easy for the patient to swallow.

35. provide the necessary bulk to completely fill the prescribed capsules
provide the necessary bulk to completely fill the prescribed capsules. The steps used in calculating the proper capsule fill may be described as follows:
Step 1. Select an appropriate capsule size.
Step 2. Fill the capsule shell separately with each drug and diluent, and record the weights of each.
Step 3. Calculate the diluent displacement weight for each drug
Step 4. Calculate the amount of diluent required per capsule.
Step 5. Calculate the total quantities of each drug and the diluent needed to fill all of the capsules prescribed.

36. Example Calculation to Determine a Capsule Fill
Determine the total quantities of each drug and lactose required to fill the following prescription.
R Drug A mg
Drug B mg
Lactose, q.s.
M.ft. caps # 20

37. Step 1. For the purpose of this example, assume the pharmacist selected a size 1 capsule.
Step 2. The pharmacist filled a capsule individually with each ingredient, weighed them, and found:
Capsule filled with drug A weighed 620 mg
Capsule filled with drug B weighed 470 mg
Capsule filled with lactose weighed 330 mg

38. Step 3. The diluent displacement weights for drugs A and B are calculated by ratio and proportion as follows:
For drug A:
For drug B: