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.
I. Regulation
The FDA established current Good Manufacturing Practices (cGMP) to ensure that minimum standards are met for drug product quality. The National Association of Boards of Pharmacy (NABP) formulated “Good Compounding Practices” that are used by many states. These can be found in the United States Pharmacopeia-National Formulary (USP-NF) and establish standards for extemporaneous compounding of nonsterile and sterile preparations.
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)?
6. Were all calculations and measurements confirmed to ensure that the preparation will be compounded accurately?
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
B. Trissel’s Stability of Compounded Formulations: The handbook of stability and compatibility of injectable products
| Binders | |
| Buffer |
Maintain the pH of a product to prevent drug degradation and can also protect the user from GI irritation
|
| Coatings |
Can protect the drug product from degradation from the environment or from the GI tract for long-acting or delayed-release
|
| Coloring agents | |
| Diluents/Fillers |
Allow for filling of a capsule or increase the size of a tablet for greater ease in handling; also used for creating aliquots or dissolving medications
|
| 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?
Penicillin VK suspension 250 mg/5 mL
Full access? Get Clinical Tree
