Procedures to compound non-sterile products

Drug compounding is often regarded as combining, mixing, or altering ingredients to create a medication tailored to an individual patient’s needs. Compounding includes the combining of two or more drugs. It may be sterile or non-sterile compounding. Sterile compounding is done under strict aseptic precautions in a clean room environment and is used for products such as intravenous infusions, eye drops, etc. Non-sterile compounding doesn’t require strict aseptic conditions and is done to create commercially unavailable drug formulations from bulk ingredients. Compounded drugs are not FDA-approved. However, local and federal laws, regulations, and USP standards must be followed while compounding medications. Federal law allows compounding by a licensed pharmacist in a state-licensed pharmacy, federal facility, or a physician, as well as compounding by or 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.

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 mentioned in “mesh size” which corresponds to the pore size of a mesh through which the particle will easily pass. Smaller the mesh size, smaller will be the particle size. Powders may contain one or more ingredients. While compounding powders, care must be taken that the particles are distributed uniformly. Reducing the particle size helps in uniform distribution. This can be done by trituration, pulverization or levigation. Trituration consists of grinding the powder to a finer size. Pulverization consists of using a solvent to dissolve the powder particles and then evaporating the solvent to get finer particles. Levigation uses a liquid in which the particles are insoluble. When one ingredient is larger in quantity than another ingredient, the geometric dilution method is used for mixing powders.
2. Tablets: Tablets are made by compressing or molding powders into a solid tablet form. In molding, the ingredients in powder form are first added to a base like lactose or sucrose, and mixtures of alcohol and water are added to moisten the particles and then it is pressed and molded into tablet form. Compressed tablets use a special machine to make tablets. The powder mixture is placed into the machine which compresses it releasing one tablet at one time.
3. Capsules: Capsules can have hard shells or soft shells. Gelatin capsules are numbered e.g. 5, 3, 0 etc. The smaller numbers correspond to larger capsule sizes. Selecting the appropriate capsule size depends on weight, density of ingredients and dose. The capsule is filled with powdered ingredients either manually or using filling devices.
4. Solutions: Solutions contain dissolved ingredients. They can be of various types like syrups, spirits and elixirs. The active ingredients are dissolved in solvent such as purified water, ethanol and propylene glycol. Other ingredients like coloring and flavoring agents, stabilizers, buffering agents and preservatives are added to maintain quality and stability.
5. Suspensions: Suspensions are composed of insoluble ingredients, hence to maintain proper dosing, the compounder has to take care that the drug is uniformly dispersed in the suspension. The solid ingredients are crushed, then they are mixed with wetting agents like glycerin, polysorbate or benzalkonium chloride, followed by adding a suitable vehicle to make a paste first which is diluted to the desired consistency. Wetting agents help to disperse the particles by reducing the surface tension. Suspending agents like methylcellulose,xanthan gum etc are added to increase the consistency. In addition, flavoring agents, stabilizers and preservatives are also added.
6. Ointments and pastes: The vehicle or base is selected depending on whether the drug needs to penetrate the skin (antiseptic) or stay on the surface (emollients). Ointment bases include greasy, water repellents (vegetable, animal and mineral oils), greasy, water absorbing bases (organic montmorillonite, lanolin) or water soluble bases (macrogol, PEG or polyethylene glycol). Pastes are stiffer than ointments. Pastes use 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 which are generally dissolved, suspended or emulsified in the base. After blending the ingredients, they are packed in airtight jars and tubes.
7. Suppositories: The active ingredient is incorporated into a base like cocoa butter, glycerinated gelatin or PEG which dissolve inside the body. After blending, the mixture is either rolled by hand or by 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.