Drug compounding means combining, mixing, or altering ingredients to prepare a medication that fits an individual patient’s needs. Compounding can include combining two or more drugs. It may be sterile or non-sterile.

• Sterile compounding is performed using strict aseptic technique in a clean room environment. It’s used for products such as intravenous infusions and eye drops.
• Non-sterile compounding doesn’t require strict aseptic conditions. It’s used to prepare drug formulations that aren’t commercially available, often from bulk ingredients.

Compounded drugs are not FDA-approved. However, compounding must follow applicable local and federal laws, regulations, and USP standards. Federal law allows compounding by:

• A licensed pharmacist in a state-licensed pharmacy, a federal facility, or by a physician
• A licensed pharmacist (or someone working under the direct supervision of a licensed pharmacist) in an outsourcing facility

General principles of compounding

1. Quality and purity of ingredients must be maintained.
2. The facility should be clean and have adequate room for storage.
3. Personnel should be appropriately trained.
4. Equipment must be clean, well-maintained, and calibrated.
5. The process should be well documented, including compounding logs and master control files. A Safety Data Sheet (SDS) should be maintained with information on safeguards and treatment of accidental exposures.
6. Establish a Beyond Use Date (BUD). A BUD is the date after which a compounded product should not be used. After the BUD, the product loses its potency, purity, and quality. In the absence of stability information for ingredients, the BUD can be roughly calculated as follows.
7. The product should be packaged and labeled correctly with appropriate storage and handling instructions.
8. Tablets and capsules should be stored in amber-colored vials to protect the product from light. Ointments and creams may be placed in white ointment jars. Suppositories and pellets may be dispensed in cardboard boxes.

Table showing how to calculate BUD for non-sterile compounding

Procedures to compound non-sterile products

1. Powders: Powders are made of particles ranging in size from 0.1-10 micron. Particle size is often described using mesh size, which corresponds to the pore size of a mesh through which the particle can pass. A smaller mesh size corresponds to smaller particles. Powders may contain one or more ingredients. During compounding, the key goal is uniform distribution of particles.

   Reducing particle size helps improve uniformity. This can be done by:

   • Trituration: grinding the powder to a finer size
   • Pulverization: dissolving powder particles in a solvent, then evaporating the solvent to obtain finer particles
   • Levigation: using a liquid in which the particles are insoluble to form a smooth paste

   When one ingredient is present in a much larger quantity than another, the geometric dilution method is used to mix powders evenly.

2. Tablets: Tablets are made by compressing or molding powders into a solid tablet form.

   • In molding, powdered ingredients are first mixed with a base such as lactose or sucrose. A mixture of alcohol and water is added to moisten the particles, and the mass is pressed and molded into tablet form.
   • Compressed tablets are made using a special machine. The powder mixture is placed into the machine, which compresses it and releases one tablet at a time.

3. Capsules: Capsules may have hard shells or soft shells. Gelatin capsules are numbered (e.g., 5, 3, 0). Smaller numbers correspond to larger capsule sizes. Selecting the appropriate capsule size depends on the weight and density of the ingredients and the required dose. Capsules are filled with powdered ingredients either manually or using filling devices.

4. Solutions: Solutions contain dissolved ingredients. Common types include syrups, spirits, and elixirs. Active ingredients are dissolved in a solvent such as purified water, ethanol, or propylene glycol. Other ingredients (such as coloring and flavoring agents, stabilizers, buffering agents, and preservatives) may be added to maintain quality and stability.

5. Suspensions: Suspensions contain insoluble ingredients. To ensure accurate dosing, the drug must be uniformly dispersed throughout the liquid.

   A typical process includes:

   • Crushing the solid ingredients
   • Mixing them with a wetting agent (e.g., glycerin, polysorbate, or benzalkonium chloride)
   • Adding a suitable vehicle to form a paste, then diluting to the desired consistency

   Wetting agents help disperse particles by reducing surface tension. Suspending agents (e.g., methylcellulose, xanthan gum) are added to increase consistency. Flavoring agents, stabilizers, and preservatives may also be included.

6. Ointments and pastes: The vehicle (base) is selected based on whether the drug should penetrate the skin (e.g., antiseptics) or remain on the surface (e.g., emollients).

   Ointment bases include:

   • Greasy, water-repellent bases (vegetable, animal, and mineral oils)
   • Greasy, water-absorbing bases (organic montmorillonite, lanolin)
   • Water-soluble bases (macrogol, PEG, or polyethylene glycol)

   Pastes are stiffer than ointments. Paste bases may include liquid or soft paraffin, glycerol, or soap bases. Pastes contain a large amount of finely powdered solids (such as starch, zinc oxide, and calcium carbonate), whereas ointments contain medications that are generally dissolved, suspended, or emulsified in the base. After blending, products are packed in airtight jars or tubes.

7. Suppositories: The active ingredient is incorporated into a base such as cocoa butter, glycerinated gelatin, or PEG, which dissolves inside the body. After blending, the mixture is either rolled by hand or prepared using molding devices.

8. Enemas: After accurately weighing and measuring dry and wet ingredients, they are mixed. Purified water is added to achieve the required dilution and volume.