CHAPTER 3 Compounding
The Federal Drug Administration (FDA) defines traditional pharmacy compounding as “the combining, mixing, or altering of ingredients to create a customized medication for an individual patient in response to a licensed practitioner’s prescription (www.fda.gov). Compounding is often used when the patient is intolerant of a manufactured drug. It may also be needed when an alternative route of administration is needed and not available commercially. It also allows physicians to prescribe customized strengths and dosage systems.
II. Quality assurance
A. Nonsterile products1: The following questions are to be considered carefully before compounding:
1. Have the physical and chemical properties and medicinal, dietary, and pharmaceutical uses of the drug substances been reviewed?
2. The first time a product was compounded, was documentation made of the materials and equipment used, method of mixing, labeling requirements, and dating determination?
4. Will the active ingredients be effectively absorbed, locally or systemically according to the prescribed purpose, from the preparation and route of administration?
5. Are there added substances, confirmed or potentially present from manufactured products, that may be expected to cause an allergic reaction, irritation, toxicity, or undesirable organoleptic response from the patient? Are there added substances, confirmed or potentially present, that may be unfavorable (e.g., unsuitable pH or inadequate solubility)?
III. Requirements for Compounding
C. Compounding area
1. The product may be flammable (e.g., alcohol), highly reactive (e.g., phenol), or cytotoxic (e.g., chemotherapy). The pharmacist may need to prepare the medication in a vertical flow hood to prevent harm to himself/herself. The pharmacist should use appropriate attire (e.g., gloves, gowns, facial covering).
IV. Achieving Stabilization of the Preparation
V. Compounded Preparations
C. Emulsions
• Emulsions are two-phase systems that consist of two immiscible liquids, one of which is uniformly dispersed throughout the other as fine droplets. They are classified as oil-in-water (o/w) or water-in-oil (w/o).There may also be multiple emulsions (e.g. w/o/w emulsion where a water droplet enclosed in an oil droplet is itself dispersed in water). They may be used internally to mask the bitter taste or odor of drugs or externally as creams or lotions.
I. Parenteral preparations
• Desired effect is systemic when substance is given by routes other than the digestive tract. Parenteral administration generally has the greatest bioavailability because it avoids an absorption phase and possible inactivation by first-pass metabolism by the liver. It can be further divided into two subgroups: parenteral by injection or infusion and other nonoral parenteral administration (transdermal patch)
VI. Examples of References Pharmacists May Use for Compounding
A. The United States Pharmacopeia–National Formulary (USP–NF): The compendium for pharmaceutical medicines and excipients for use in the United States
| Binders | |
| Buffer | |
| Coatings | |
| Coloring agents | |
| Diluents/Fillers | |
| Emulsifiers | |
| Flavoring agents | |
| Preservatives | |
| Antioxidants | |
| Alcohols | |
| Parabens | |
| Chelators | |
| Sweeteners |
| Aliquot | A stock product made for a quantity below the least measurable quantity; see also least measurable quantity |
| Aseptic technique | The process of making a sterile product while reducing contamination of any particles, pathogens, or pyrogens; particularly important for parenteral, ophthalmic, and inhaled preparations |
| Biologic safety cabinet | A work area designed to aseptically prepare sterile medications; the vertical flow hood is ideal for preparing chemotherapeutic drugs, volatile substances, and other cytotoxic medications; the horizontal flow provides no protection to the user |
| Eutectic mixture | The combination of two solid substances at room temperature, which become liquid when combined |
| Geometric dilution | Mixing two powders of unequal size |
| Infusion (herbal medicine) | The steeping of a medicine in water; making a tea |
| Infusion (modern medicine) | Continuous delivery of a solution over a prolonged period of time |
| Least measurable quantity | The smallest amount that can be quantified by a scale or other measuring device; if a quantity must be used for which the device cannot measure, an aliquot must be made |
| Levigate | To make into a smooth, fine powder or paste, as by grinding when moist |
| Liniment | A liquid or semifluid preparation that is applied to the skin as a counterirritant |
| Mortar | A bowl for grinding and mixing ingredients |
| Muddle | The process of grinding a solid in a mortar with a pestle into a fine powder |
| Pestle | A rod used to grind and mix ingredients |
| Spatulation | Blending small amounts of powder by movement of a spatula on a paper or tile |
| Topical | A dosage form meant to treat an affected area without systemic effects |
| Transdermal | A medicated adhesive patch that is placed on the skin to deliver a time-released dose of medication through the skin and into the bloodstream; not to be confused with a topical medication |
| Triturate | To rub, crush, grind, or pound into fine particles or a powder; pulverize; also known as muddling |
REVIEW QUESTIONS
(Answers and Rationales on page 317.)
1. What is the percent weight/weight (w/w) if 250 grams of dextrose is dissolved in 300 mL of water to make a final volume of 500 mL?
2. How many day’s worth of medication is provided by the following prescription?
3. What volume was dispensed by the pharmacist if the percent concentration (weight/volume) of cefaclor was 3.7%?
4. To prepare a 2% w/w hydrocortisone cream, how many grams of pure hydrocortisone powder must be mixed with 30 g of 1% hydrocortisone cream?
5. What is the final concentration (w/w) of zinc oxide ointment when 200 g of a 5% zinc oxide ointment and 400 g of a 10% zinc oxide ointment are mixed?
6. A pharmacist is asked to compound a 200 mL mixture containing maldroxyl 50 mL, diphenhydramine elixir 50 mL, and viscous lidocaine 2%. How much viscous lidocaine 2% is needed to prepare the order?
7. A pharmacist is trying to make 10% w/w sodium chloride solution and has 1 lb of 28% w/w sodium chloride solution on hand. How many grams of 10% w/w sodium chloride solution can be made from the amount on hand?
8. A pharmacist is to prepare 500 g of an ointment containing 5% w/w glycerin. The density of glycerin is 1.25 g/mL. How many milliliters of glycerin are needed to prepare this formulation?
9. A pharmacist wants to prepare 4 L of 10% w/v hydrochloric acid from a stock bottle of 36.8% w/w hydrochloric acid (specific gravity 1.19). How many milliliters of the stock solution should be used to prepare the final 10% w/v hydrochloric acid solution?
10. A compounding pharmacy gets an order for 2 lb of 2% mupirocin ointment. The stock ointment on hand is 5% mupirocin ointment. How many grams of the 5% formulation should be mixed with white petrolatum in order to prepare this order?
13. Sodium fluoride 250 mcg
How many milligrams of sodium fluoride are required to prepare the prescription?
15. For a 23-year-old female patient:
Lactose will be the preferred filler agent because of its solubility. The appropriate capsule size for the above prescription will be capsule size #1 with an approximate capacity of 0.5 mL. The tapped density of the ingredients are as follows: diphenhydramine 800 mg/mL, acetaminophen 850 mg/mL, and lactose 950 mg/mL. Determine the amount of lactose needed to prepare this prescription.
17. Which of the following statements about laminar flow hoods are FALSE?
II. Laminar flow hoods provide a constant flow of air out of the work area to prevent room air from entering.
III. The air flowing out from the hood suspends and removes contaminants introduced into the work area by personnel.
18. Objects in the hood are arranged in a manner to get full benefit of the laminar flow of air. In a horizontal hood, the items should be placed:
a. individually left to right, equidistance from the front and back of the laminar airflow hood working space as well as from each other
20. Which of the following statements about laminar flow hoods are FALSE?
II. Laminar flow hoods provide a constant flow of air out of the work area to prevent room air from entering.
21. To remove 5 mL of solution from a 30-mL multidose vial, what is the correct order of steps?
23. Needle size is determined by the gauge and the length. Which of the following statements are correct?
24. A concentrated vancomycin solution of 10 mL is added to a 100 mL piggyback bag of normal saline. The solution is to be infused over one hour. What is the infusion rate?
25. How many milliliters of water should be mixed with 120 mL of syrup containing 75% w/v sucrose to make a syrup containing 50% w/v sucrose?
26. Which of the following statements is INCORRECT?
a. To prevent contamination, swab rubber closure of the vial with 70% alcohol using firm strokes in any direction or manner.
b. To prevent core formation, insert needle to penetrate the rubber closure at same point with both tip and heel of bevel.
29. True or False: When preparing a dose from an ampule, one should use a 0.22-μm inline filter rather than the 5-μm filter straw.
30. True or False: Nitroglycerin should always be prepared in glass because it is adsorbed to polyvinyl chloride (PVC), the plastic in the bags, and intravenous (IV) tubing.
31. Drugs that are adsorbed to the inner lining of IV containers and tubing or administration sets, resulting in loss of drug delivered to the patient, include:
35. Answer the question based on the following prescription:
37. Medicinal agents can either be weak acids or weak bases. Weak bases include the following EXCEPT:
40. Which of the following statements is FALSE?
47. Needle size is determined by the gauge and the length. Which of the following statements is/are correct?
48. When obtaining a 3-mL dose from a 5-mL ampule, which one of the following steps is INCORRECT?
49. If the infusion rate for drug X is 120 mL/hr, what is the infusion rate in drops (gtt) per minute if drug X is administered using an infusion set that delivers 20 gtt/mL?
50. The pharmacist needs to prepare 100 capsules, each containing 4 mg of estriol and 0.5 mg of estradiol. A size 3 capsule is chosen for the prescription and separate capsules are filled with drug and lactose. Weights of contents are as follows: estriol = 250 mg, estradiol = 180 mg, lactose = 300 mg
How much of each ingredient are needed to prepare this prescription.
52. Lactose, microcrystalline cellulose, and starch are commonly used:
53. The total fill weight (drug plus excipients) for one capsule of a prescription was determined to be 280 mg. Which of the following choices is/are appropriate?
54. Question refers to the following prescription:
59. How many grams of coal tar must be incorporated into 450 grams of zinc oxide paste to prepare a 10% coal tar ointment?
