The Pharmaceutics and Compounding Laboratory
Sterile Compounding


This route of administration is generally considered less hazardous and easier to use than the intravenous route. The onset of action is typically longer than with intravenous administration, but shorter than with subcutaneous administration. Patients generally experience more pain via intramuscular administration compared to intravenous administration.

Intramuscular (IM) injections are made into the striated muscle fibers that are under the subcutaneous layer of the skin. Thus needles used for the injections are generally 1 inch to 1.5 inches long and are generally 19 to 22 gauge in size. The principal sites of injection are the gluteal (buttocks), deltoid (upper arm), and vastus lateralis (thigh) muscles. When administering intramuscular injections into the gluteus maximus, the size of the needle must be chosen based on the patient's deposits of fat. If a needle is used that is too short to pass all the way through the fat into the muscle, then the injection will be made into the fat. Women tend to have more fat in this region than men, so the possibility of a intralipomatous injection is significant. It is estimated that few women and about 15% of men actually receive the intended intramuscular injection because an improper needle length was used.

If a series of injections are to be given, the injection site is usually varied or rotated. Generally only limited injection volumes can be given by intramuscular injection: 2 ml in the deltoid and thigh muscles, and up to 5 ml in the gluteus maximus.

The point of injection should be as far as possible from major nerves and blood vessels to avoid neural damage and accidental intravenous administration. To insure that a blood vessel has not been entered, the syringe should be slightly aspirated after insertion and before injection to see if blood enters the syringe. Other injuries that can occur following intramuscular injection are abscesses, cysts, embolism, hematoma, skin sloughing, and scar formation.

The Z-tract injection technique is useful for medications that stain upper tissue such as iron dextran or drugs that irritate tissues such as diazepam. The skin is laterally displaced prior to injection, the needle is inserted, and the injection is performed. The needle then is withdrawn and the skin released. This creates a "Z" pattern that blocks infiltration of the drug into the subcutaneous tissue. These injections are generally 2-3 inches deep.

Intramuscular injections generally result in lower but more sustained blood concentrations than after intravenous administration. Part of the reason is that intramuscular injections require an absorption step which delays the time to peak concentrations. When a formulation is injected, a "depot" forms inside the muscle tissue which acts as a repository for the drug. The absorption rate from this depot is dependent on many physiological factors such as muscle exercise, depth of injection, local blood flow supply, etc.

The absorption rate from the depot is also influenced by many formulation factors. Aqueous solutions typically provide the fastest absorption possible from the IM depot and oleaginous solutions provide slightly slower absorption. But to further alter the absorption rate, drugs are formulated as suspension or colloids in aqueous and oleaginous solvents or as oil-in-water emulsions and water-in-oil emulsions. Different salt forms of the drug may also be used to take advantage of a slower dissolution rate or a lower solubility inherent with the salt. All of these factors can be varied to achieve the desired absorption rate. For example, to achieve a very slow absorption rate, a low solubility salt form of the drug could be placed as a suspension in an oleaginous solvent. Here the salt would slowly dissolve due to it limited solubility, and then slowly diffuse through the oleaginous solvent.

Or another approach could be to make large particles of the drug (which will dissolve slowly) and put them in the oil phase of an oil in water emulsion. In this case, the drug would dissolve slowly, but would also diffuse slowly out of the oil phase, and would still need more time to diffuse through the water phase of the emulsion. Thus, there are three processes that influence the absorption rate of this type of formulation.