The Pharmaceutics and Compounding Laboratory
Sterile Compounding

Subcutaneous

The subcutaneous (SC, SQ) route is one of the most versatile routes of administration in that it can be used for both short term and very long term therapies. The injection of a drug or the implantation of a device beneath the surface of the skin is made in the loose interstitial tissues of the upper arm, the anterior surface of the thigh, or the lower portion of the abdomen. The upper back also can be used as a site of subcutaneous administration. The site of injection is usually rotated when injections are frequently given. The maximum amount of medication that can be subcutaneously injected is about 2 ml. Needles are generally 3/8 to 1 inch in length and 24 to 27 gauge.

Absorption of drugs from the subcutaneous tissue is influenced by the same factors that determine the rate of absorption from intramuscular sites (slowly soluble salt forms, suspensions versus solutions, differences in particle size, viscosity of the injection vehicle, etc.); however, the vascularity in the subcutaneous tissue is less than that of muscle tissue, and therefore absorption may be slower than after intramuscular administration. But absorption after subcutaneous administration is generally more rapid and predictable than after oral administration. There are several ways to change the absorption rate:

  • use heat or massage the site to increase the absorption rates of many drugs.
  • co-administer vasodilators or hyaluronidase to increase absorption rates of some drugs. Conversely, epinephrine decreases blood flow which can decrease the absorption rate.

Many different solution and suspension formulations are given subcutaneously. Heparin, enoxaparin, and insulin are the most important drugs routinely administered by this route. Drugs that are administered by the route must be soluble and potent in small concentrations since only a very small volume can be injected.

In spite of the advantages of this route of administration, there are some precautions to observe.

  • Drugs which are irritating or those in very viscous (thick) suspensions may produce induration, sloughing, or abscess formation and may be painful to the patient.
  • Irritating drugs and vasoconstrictors can lead to abscesses or necrosis.
  • If frequent injections are required, the injection sites must be rotated.

One of the most obvious ways to achieve very long term drug release is to place the drug in a delivery system or device that can be implanted into a body tissue. The subcutaneous tissue is the ideal site for implantation of such devices. Implantation often requires a surgical procedure or a specialized injection device. The fact that the device will be in constant contact with the subcutaneous tissue requires that the device materials be biocompatible (e.g., not irritating) and do not promote infection or sterile abscess. Another advantage is that the device can be easily removed if necessary.

Examples of implantable devices are Norplant®, Oreton®, Percorten® and an osmotically driven mini-pump (Alzet®) which can deliver drug solutions for up to twenty-one days. Many devices provide drug release for months or years. ViadurTM DUROS® implants are made from a titanium alloy and are capable of delivering the drug for up to one year. Supprelin LA® implants are also able to provide drug release for up to one year. Implanon® and Nexplanon® release a drug for three years and are used as contraceptives. Other devices include degradable microspheres, vapor pressure devices for morphine release, osmotic pressure devices to deliver insulin, and magnetically or ultrasonically activated pellets.

Sometimes ports and pumps are placed in the subcutaneous space and the attached delivery catheter is placed in a vein, cavity, or artery.