The principal method of giving drugs is by mouth (oral route), and doses which are not otherwise specified are assumed to be oral doses. The important site of drug administration is the parenteral method, which includes all forms of injections. These may be classified as follows:
- Subcutaneous (s.c)– an injection made by inserting the hypodermic needle through the layers of the skin into the areolar tissue, produces a prompt response. The dose of drug is usually about half of that required orally.
- Intramuscular– an injection made by inserting needle through the layers of the skin deep into skeletal muscles, permits the parenteral administration of finely divided insoluble substances in suspension. The onset of action is slow, but duration of action is prolonged. A depot of the medicament (oily solutions, aqueous suspensions) is deposited in the muscle by injection and slow absorption occurs.
- Intravenous (i.v)– an injection made directly into the vein and elicits a very rapid response. The drug is instantly carried to the tissues upon which it is to act. Many substances that are very harmful to the surrounding tissues can be injected into the blood.
- Intrathecal– an injection made by inserting needle through the interspinous spaces into the spinal fluid. These are used for the drugs which do not find their way into the spinal fluid. In infectious types of meningitis this kind of injection is useful. The production of spinal anesthesia is dependent upon the intrathecal injection of the spinal anesthetic into the subarachnoid space.
- Bone marrow– an injection made by inserting needle into the marrow of the sternum or other bones. These are occasionally utilized when the veins are unavailable on account of their size. the bone marrow injection gives almost the same effect as compare to intravenous injection.
- Intraperitoneal– an injection into the peritoneal cavity. Intraperitoneal injections are employed when veins are not available for an intravenous injection. It affords rapid absorption.
All of these forms of parenteral administration have their specific advantages.
- Gastric irritation, nausea and vomiting are not provoked.
- 100% bioavailability is achieved.
- These routes can be employed in unconscious patients.
- Onset of action is very rapid.
- There is no interference of gastric juices and liver is bypassed.
Disadvantages of these routes are:
- Self-administration is not possible
- Administration is painful
- Chances of local tissue injury
Many drugs are most rapidly absorbed from mucosal cells. The mucosa, therefore, provides an excellent method of administrating certain drugs. The tablets of glyceryl trinitrate are administered under the tongue in the treatment of angina pain (sublingual route). Absorption is so fast that relief begins within 1-5 minutes after the tablet is placed under the tongue. This route bypasses the portal circulation.
The rectal absorption of drugs is also prompt and efficacious. Suppositories may be employed for this purpose. Hypnotic drugs are given rectally.
The nasal septum quite readily absorbs certain drugs placed upon it. Nasal decongestant agents are used in this route.
Inhalation. Volatile compound may readily be administered by inhalation. Gaseous and volatile liquid anaesthetics are administered in this manner. Inhalation therapy is prompt; contact with blood through the alveolar membrane is abundant. Absorption takes place from the large surface of alveoli-action is very rapid.
PRINCIPLES OF INTESTINAL ABSORPTION
Most drugs are absorbed from the small intestines. The process of absorption is governed by:
- The chemical nature of the drug
- The relative solubility of drug in water and lipids.
- The diffusion of drug through cellular membranes
- The acidity and alkalinity of the substance
The barrier between the blood and gastric juice behaves toward drugs like a lipoid film. Weakly dissociated acids are well absorbed, whereas strongly dissociated acids are poorly absorbed from the gastric juice. It is clear that large protein molecules are not absorbed from gastrointestinal tract. Insulin, a large protein molecule, undergoes degradation by the digestive enzymes; hence it is not active when administered orally.
Soluble iron salts like ferrous sulphate are readily absorbed upon oral administered. Aluminium salts do not penetrate the mucosal barrier. The mucosal barrier does not behave like fine sieve. Absorption is shown to be favoured by oil solubility. As a rule drugs which are not soluble in oil and water such a as barium sulphate and aluminium hydroxide are not absorbed rom the gastrointestinal tract.
Although most drugs are absorbed from the small intestines, absorption may occur from the colon. The passage of drug from the gastrointestinal tract into the circulation does not assure its penetration of blood-brain barrier and entrance into the central nervous system. The drug may be well distributed in other organs, yet it may not enter the brain or the cerebrospinal fluid or may possibly be present to a very limited extent.
As most of the drugs are administered orally, however here are limitations of this route.
- Most of the drugs undergo through the pass metabolism.
- May cause gastric irritation, nausea and vomiting.
- Some drugs are destroyed by gastric juices.
- 100% bioavailability is not possible.
- Onset of action is not rapid as compared to intravenous administration.
- Nauseating drugs are difficult to swallow.
Certain drugs are applied locally on skin for dermal absorption. Stratum corneum is lipid barrier for skin absorption of drugs. The stratum corneum (or the horny layer) is the top layer of the skin and varies in thickness from approximately 10 microns to several hundred microns, depending on the region of the body. Absorption of drugs through the skin is proportional to lipid solubility. Dosage forms like creams, ointments, lotions, liniments are used for this route.
FUNDAMENTAL OF SKIN PERMEATION
As Skin is impermeable barrier and it is found that lipid – soluble substances such as nonelectrolyte have comparatively greater skin permeability than water soluble substances like electrolytes. The various skin layers are not equally permeable. The epidermis is much less permeable than dermis. The stratum corneum is essentially a uniformly good permeation barrier. Outer layer of the skin greatly delays permeation.
This route is beneficial for drugs whose systemic absorption from these sites is very less or absent. Thus high concentrations are achieved at the desired site without exposing rest of the body. For some drugs in suitable dosage forms that are absorbed from local routes may serve as systemic routes of administration for example, transdermal patches. These are dosage forms that provide 100% bioavailability as that of intravenous administration.
Transdermal delivery systems are topically administered preparations in the form of patches or film that gives systemic delivery at controlled rate.
- Bypass of first pass metabolism
- Controlled and stable blood levels
- Long duration of action
- Self-administration is possible.
- Dosage forms which cause irritation in other route, or have very short half-life, narrow therapeutic window can be converted into transdermal patches.
Transdermal patches are available in various shapes and sizes which can be applied directly on skin usually chest, upper arm, abdomen, lower back, and buttock.
CHOICE OF ROUTE FOR ADMINISTERING DRUGS/FACTORS GOVERNING
- Site of desired action eg. Lungs or local
- Onset of action or rapidity at which the effect is desired
- Patient’s condition
- Selective action eg anaesthesia
- Physical and chemical properties of the drugs.