DRUG ABSORPTION

Systemic Versus Local Administration

drugs are given to patients at locations of the body called sites of administration. The overall goal is for the drug to travel from the site of administration and reach its site of action in a time and predictable manner, where it can perform, its functions.

The choice of administration method depends on, among other factors, the physicological limitations of the administration or absorpsion site, and the clinical situation.

The site of action is generally not a single location, or is difficult to reach. In such situations the drug is administered at some convenient location far removed from the site of aaction. In some situations, the site of action is localized and is readily accessible; in these cases the drug can be admnistered very close to or right at this site. Such an approach to drug administration is termed topical, nonsystemic, or local administration.

Systemic Administration
Systemically administerd drugs may be absorbed from the site of administration. Table of Classification of the Available Routes Of Administration for Drugs Systemic Oral Parenteral : 1. Intravenous 2. Intramuscular 3. Subcutaneous 4. Intraarterial Rectal Sublingual/buccal Transdermal Pulmonary Nasal Rectal Buccal Dermal Pulmonary Nasal Ophthalmic Vaginal/urethral Oral Parenteral : 1. intracardiac 2. intratechal 3. intralumbar Nonsystemic

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patches, from which the drug is absorbed through the skin where it is administered. In other cases, the drug moves from the site of administration to a different region called the site of absorption.

1. Rate of Absorption Rate of absorpsion into the bloodstream depends on physicochemical properties of the drug, permeability of the epithelial membrane at the site of absorption, surface area of the membrane exposed to drug at the absorption site, and concentration gradient of drug between the absorption site and the bloodstrea. The equation for the rate of absorption is similar to Ficks law of diffusion: P.A.D. (Ca Cp) Absorption rate = h (Eq. 9. 1)

The partition coefficient P and diffusion coefficient D depend on the structure of the drug. The term A refers to the surface area of the membrane, and the term h is the thickness of the epithelial membrane at the absorption site, this membrane may be composed of one or several layers of epithelial cells.

2. The Oral Route Oral administration, in which a drug product is adminestered by mouth and swallowed, is the most common and preffered route of systemic administration. The drug moves down to Gastrointestinal (GI) tract, and can be absorbed in any of several regions.

Structure of the Gastrointestinal Tract The primary organs of the GI tract are the stomach, the small intestinen(made up of the duodenum, jejunum, and ileum), and the colon (large intestine). The GI tract ends in the rectum. The various part differ from each other in structure, size, secretions, and pH, all of which influence drug absorption. Although an orally administered product starts in the mouth and travels down the esophagus, the drug spends so little time here that the esophagus has no significant role in absorption of oral medications.

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*. Diagram of the esophagus and gastrointestinal tract, showing the different part

Bloodstream to the rest of the body. Epithelial cells of the mucosa are closely packed with very tight junctions. The diameter of these gaps has been estimated to be about 1.5 nm, too small for most drugs to cross paracellularly.

The Stomach. An orally adminestered drug product arrives in the stomach after administration. The stomach is a pouch like organ whose primary purpose is to grind food and mix it with acidic gastric fluid. The empty stomach contains approxinately 100 ml of gastric fluid ; its maximum capacity is about 1 L. The mucosa lining the stomach is composed of cells that secret mucus, hydrocholoric acid, and digestive enzymes, all of which make up gastric fluid.

The Small Intestine. The intestinal ephitelium, or gut wall, acts as a barrier between two compositionally distinct compartment-the gut lumen and blood. Maintenance of this barrier is required for protection of the body from pathogens and toxins.

The Large Intestine. The large intestine or colon is structually similar to the small intestines but does not have villion on its inside surface, limiting the surface area available for absorption. The main absorptive function of the colon is absorption of water and electrolytes into the circulation. For example, theophylline is partially absorbed from the colon. In general, if a large amount of unabsorbed drug reaches the colon, it is excreted inn the feces.

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ORAL DRUG ABSORPTION

As a result of surface area and residence time constraints, the small intestines are the main site for drug absorption. 1. Passive trancellular diffusion Only uncharged drugs and un-ionized forms of weak acids and weak bases can cross the intestinal epithelium by passive diffusion.

Typicaal pH Values of the Various Regions of the Human GI Tract No 1 2 3 4 5 6 7 8 Mouth Esophagus Stomach Duodenum Jejunum Ileum Colon Rectum GI Region Normal pH 6,5 - 7,0 5,0 6,0 1,0 3,5 5,5 6,5 6,5 7,0 7,0 7,5 6,0 7,0 7,0 7,5

2. Carrier Mediated Absorption. Many ions and nutrients (such as amino acids, small peptides, vitamins, minerals, and sugars) are absorbed from the GI tract via selective transporters present on the ephitelial cell membrane and in the brush border region of the small intestines. 3. Intestinal Drug Efflux. The role of non specific multidrug resistance (MDR) transporters as efflux pumps is becoming increasingly important in understanding the poor oral absorption af a variety of drugs. 4. Transcytosis. Transcystosis is relatively uncommon for the absorption of drugs from the GI tract because most drugs are small molecules.

Nonoral Routes for Systemic Administration

1. The Parenteral Route 2. The Rectal Tube 3. The Buccal or Sublingual Route 4. The Transdermal Route 5. The Pulmonary Route 6. The Nasal Route

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Absorption of Macromolecular Drugs

Proteins and other macromolecules present a difficult delivery problem, not only because of their large size but also because of their extreme sensitivity to the surrounding environment. Parenteral administration is still the most common route of delivery. The pulmonary route has shown success with macromolekular drugs delivered either as solutions or fine powders. The properties and composition of lung fluid are similar to those of blood, so pulmonary delivery is very similar to injection into the bloodstream.

Local Administration
Local administration is usually rather inefficient in that only 5 to 15% of applied drug reaches the site of action. Nevertheless, high local tissue concentrations are achieved, usually much higher than those possible by a sistemic route.

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