A by anatomical ways is shown in Table 1.1

A drug delivery system (DDS) is definedas a formulation or a device that enables the introduction of a pharmaceuticalcompound in human beings to achieve therapeutical effects and improve itsefficacy and safety by controlling the speed and the place of release of drugsin the body. The term pharmaceutical compound also applies to an agent such asgene therapy that will induce in vivo production of the active therapeuticagent. Gene therapy can fit in the basic and broad definition of a drugdelivery system. Gene vectors may need to be introduced into the human body bynovel delivery methods. Various routes of drug delivery systemDrugs can be administered intothe human body by various anatomical ways.

They may be intended for systemiceffects or targeted to various organs and diseases. Drugs may be administereddirectly to the organ affected by the disease or given systemically andtargeted to the diseased organ. The choice of the way of administration dependson the effect desired, the disease and the chemical formulation of the product.A classification of various routes of systemic drug delivery by anatomical waysis shown in Table 1.1 Oral Drug DeliveryThe oral route of drug administration hasbeen, generally, the most used for both traditional as well as novel drugdelivery.

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The reasons for this preference are obvious because of the ease ofadministration and widespread acceptance by patients. However, the oral drugdelivery system has many limitations such as:ü Sustained release and controlled-releasesystems due to the variation of the absorption rates and the serum concentrationswhich may be unpredictable.ü The high level of acid in the digestivetract can degrade some drugs well before they reach the site of absorption intothe bloodstream.

This is a particular problem for ingested proteins. Therefore,this route has limitations for administration of biotechnology products.ü Many compounds cannot effectively traversethe cells of the epithelial membrane in the small intestines to reach thebloodstream. Their use is limited to local effect in the gastrointestinal tractand also some drugs irritate the gastrointestinal tract and this is partiallycounteracted by coating.ü Many drugs become insoluble at the low pHlevels encountered in the digestive tract. Since only the soluble form of thedrug can be absorbed into the bloodstream, the transition of the drug to theinsoluble form can significantly reduce his bioavailability.ü Oral route is not suitable for drugstargeted to specific organs.Nowadays, many researchers still trying tomake several modifications in the formulation of drugs for oral delivery forimproving their action.

 Parenteral Drug DeliveryParenteral literally means introduction ofsubstances into the body by injection of substances by subcutaneous,intramuscular, intravenous, and intra-arterial routes. Injections made intospecific organs of the body for targeted drug delivery will be described undervarious therapeutic areas. Parenteral administration of the drugs is the mostcommonly used method of drug delivery.

Many important drugs are available onlyin parenteral form.  Advantages of parenteral administration   Major drawbacks of parenteral administration   Rapid onset of action.   Injection is not an ideal method of delivery because of pain involved and patient compliance becomes a major problem. Predictable and almost complete bioavailability.

  Injections have limitations for the delivery of protein products, particularly those that require sustained levels. Avoidance of the gastrointestinal tract with problems of oral drug administration.   Provides a reliable route for drug administration in very ill and comatose patients, who are not able to ingest anything orally.     Transdermal Drug DeliveryTransdermal drug delivery is an approachused to deliver drugs through the skin for therapeutic use as an alternative tooral, parenteral routes. It includes the following categories of drugadministration:ü Local application formulations (transdermal gels)ü Drug carriers (liposomes and nanoparticles)ü Transdermal patches and transdermalelectrotransportü Use of physical modalities to facilitatetransdermal drug transportAdetailed description of technologies and commercial aspects of development aredescribed in a special report on this topic 1.Transmucosal Drug DeliveryMucous membrane covers all the internal orificesof the body such as buccal, nasal, rectal, and drugs can be introduced atvarious anatomical sites. Movement of penetrants across the mucous membranes isby diffusion.

As in the epidermis of the skin, the pathways of permeationthrough the epithelial barriers are intercellular rather than intracellular. Deliveryof biopharmaceuticals across mucosal surfaces may offer several advantages overinjection techniques, which include the following:1. Avoidance of an injection2. Increase of therapeutic efficiency3.

Possibility of administering peptides4. Rapid absorption when compared with oraladministration5. Bypassing first pass metabolism by theliver6. Higher patient acceptance when comparedwith injectables The ideal vehicle is the one in which thedrug is minimally soluble. attractive features of buccal drug administration   Limitations to the use of buccal route Quick absorption into the systemic circulation The tablet must be kept in place and not chewed or swallowed. The tablet can be removed in case of an undesirable effect.

  Excessive salivary flow may cause a very rapid dissolution and absorption of the tablet or wash it away. Oral mucosal absorption avoids the first pass hepatic metabolism.   A bad-tasting tablet will have a low patient acceptability. A tablet can remain for a prolonged period in the buccal cavity, which enables development of formulations with sustained-release effect.

  Some of these disadvantages have been overcome by the use of a patch containing the drug that is applied to the buccal mucosa or by using the drug as a spray. This route can be used in patients with swallowing difficulties.   The tablet must be kept in place and not chewed or swallowed.  Nasal Drug DeliveryDrugs have been administered nasally forseveral years both for topical and systemic effect.

Topical administrationincludes agents for the treatment of nasal congestion, rhinitis, sinusitis, andrelated allergic and other chronic conditions. Various medications includecorticosteroids, antihistaminics, anticholinergics, and vasoconstrictors. The focusin recent years has been on the use of nasal route for systemic drug delivery. Intranasal drug delivery. Intranasal route is considered for drugsthat are ineffective orally, are used chronically, require small doses, andwhere rapid entry into the circulation is desired. The rate of diffusion of thecompounds through the nasal mucous membranes, like other biological membranes,is influenced by the physicochemical properties of the compound. However, invivo nasal absorption of compounds of molecular weight less than 300 is not significantlyinfluenced by the physicochemical properties of the drug. Factors such as thesize of the molecule and the ability of the compound to hydrogen bond with thecomponent of the membrane are more important than lipophilicity and ionizationstate.

The absorption of drugs from the nasal mucosa most probably takes placevia the aqueous channels of the membrane. Therefore, as long as the drug is in solutionand the molecular size is small, the drug will be absorbed rapidly via theaqueous path of the membrane. The absorption from the nasal cavity decreases asthe molecular size increases.Nasal drug absorption can be accomplishedby use of prodrugs, chemical modification of the parent molecule, and use ofphysical methods of increasing permeability. Special excipient used in thenasal preparations comes into contact with the nasal mucosa and may exert someeffect to facilitate the drug transport.

The mucosal pores are easier to openthan those in the epidermis. Alternative means that help overcome thesenasal barriers are currently in development. Absorption enhancers such asphospholipids and surfactants are constantly used, but care Advantages of nasal drug delivery Disadvantages of nasal drug delivery High permeability of the nasal mucosa, compared with the epidermis or the gastrointestinal mucosa Diseases conditions of the nose may result in impaired absorption. Highly vascularized subepithelial tissue Dose is limited because of relatively small area available for absorption. Rapid absorption, usually within half an hour Time available for absorption is limited.

Avoidance of first pass effect that occurs after absorption of drugs from the gastrointestinal tract Little is known of the effect of common cold on transnasal drug delivery, and it is likely that instilling a drug into a blocked nose or a nose with surplus of watery rhinorrhea may expel the medication from the nose. Avoidance of the effects of gastric stasis and vomiting, for example, in migraine patients The nasal route of delivery is not applicable to all drugs. Polar drugs and some macromolecules are not absorbed in sufficient concentration because of poor membrane permeability, rapid clearance, and enzymatic degradation into the nasal cavity.

Ease of administration by the patients, who are usually familiar with nasal drops and sprays   Higher bioavailability of the drugs than in the case of gastrointestinal route or pulmonary route    Drug delivery systems, including liposomes,cyclodextrins, and micro- and nanoparticles are being investigated to increasethe bioavailability of drugs delivered intranasally 2.After a consideration of advantages as wellas disadvantages, nasal drug delivery turns out to be a promising route ofdelivery and competes with pulmonary drug, which is also showing greatpotential. One of the important points is the almost complete bioavailabilityand precision of dosage.

 Colorectal Drug DeliveryAlthough drug administration to the rectumin human beings dates back to 1,500 B.C., majority of pharmaceutical consumersare reluctant to administer drugs directly by this route.

However, the colon isa suitable site for the safe and slow absorption of drugs which are targeted atthe large intestine or designed to act systematically. Although the colon has alower absorption capacity than the small intestine, ingested materials remainin the colon for a much longer time. Food passes through the small intestinewithin a few hours but it remains in the colon for 2–3 days.

Basic requirementsof drug delivery to the colorectal area are as follows:1. The drug should be delivered to thecolon either in a slow release or targeted form ingested orally or introduceddirectly by an enema or rectal suppository.2.

The drug must overcome the physicalbarrier of the colonic mucous.3. Drugs must survive metabolictransformation by numerous bacterial species resident in the colon, which aremainly anaerobes and possess a wide range of enzymatic activities. Drugs administered by rectal route. Advantages of the rectal route for drugadministration are as follows:1. A relatively large amount of the drugcan be administered.2.

Oral delivery of drugs that aredestroyed by the stomach acid and/or metabolized by pancreatic enzymes.3. This route is safe and convenientparticularly for the infants and the elderly.4. This route is useful in the treatment ofemergencies such as seizures in infants when the intravenous route is notavailable.

5. The rate of drug absorption from therectum is not influenced by ingestion of food or rate of gastric emptying.6.

The effect of various adjuvants isgenerally more effective in the rectum than in the upper part of thegastrointestinal tract.7. Drugs absorbed from the lower part ofthe rectum bypass the liver.8. Degradation of the drugs is much less inthe rectal lumen than in the upper gastrointestinal tract.

Disadvantages of the rectal route for drugadministration are as follows:1. Some hydrophilic drugs such asantibiotics and peptide drugs are not easily absorbed from the rectum andabsorption enhancers are required.2. Drugs may cause rectal irritation andsometimes proctitis with ulceration and bleeding. Drugs targeted for action inthe colon can also be administered orally.

Oral drug delivery to the colon hasattracted significant attention during the past 20 years. Colon targeting isrecognized to have several therapeutic advantages, such as the oral delivery ofdrugs that are destroyed by the stomach acid and/or metabolized by pancreaticenzymes. Sustained colonic release of drugs can be useful in the treatment ofnocturnal asthma, angina, and arthritis. Local treatment of colonic pathologies,such as ulcerative colitis, colorectal cancer, and Crohn’s disease, is moreeffective with the delivery of drugs to the affected area 3.

Likewise, colonicdelivery of vermicides and colonic diagnostic agents requires smaller doses.  Pulmonary Drug DeliveryAlthough aerosols of various forms fortreatment of respiratory disorders have been in use since the middle of thetwentieth century, the interest in the use of pulmonary route for systemic drugdelivery is recent. Interest in this approach has been further stimulated bythe demonstration of potential utility of lung as a portal for entry of peptidesand the feasibility of gene therapy for cystic fibrosis. It is important to understandthe mechanism of macromolecule absorption by the lungs for an effective use ofthis route.Large surface area available forabsorption. ? Close proximity to blood fl ow. ? Avoidance of fi rst-passhepatic metabolism.

? Smaller doses are required than by the oral route toachieve equivalent therapeutic effects. ? The lungs have an effi cientaerodynamic fi lter which must be overcome for effective drug deposition tooccur. ? The mucous lining the pulmonary airways clears the deposited particlestoward the throat. ? Only 10–40 % of the drug leaving an inhalation device isusually deposited in the lungs by using conventional devices.