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BY M.V. UMA MAHESHWARI DEPARTMENT OF PHARMACEUTICS

ABSORPTION OF DRUG FROM NON-PER ORAL ROUTES

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Drug absorption from all non-oral extra vascular sites is governed by the same factors that influence absorption from GIT.

This is so because the barrier to transport of drugs into to the systemic circulation from all such sites is a lipoidal membrane similar to the GI barrier .

The major mechanism in the absorption is passive diffusion.

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Ocular delivery Nasolacrimal

drainage system

Nose

NasalDelivery

PulmonaryDelivery

Buccal, sublingual gingival

Rectal delivery(lower half)Vaginaldelivery

Nasalepithelium

Respiratorymembrane

Oralmucosa

Rectal mucosa

Vaginalmucosa

SYSTEMICCIRCULATION

Oral delivery

Presystemic elimination

Liver

G-I absorption

Mucosal delivery

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SUBLINGUAL / BUCCAL ROUTESUBLINGUAL ROUTE: the dosage form is placed beneath the tongue.

BUCCAL ROUTE: Dosage form is placed between the cheek and teeth or In the cheek pouch.

Drugs administered by this route are supposed to produce systemic drug effects, and consequently, they must have good absorption from oral mucosa.

Oral mucosal regions are highly vascularised therefore rapid onset of action is observed.For Eg, anti-anginal drug Nitroglycerin.

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Blood perfuses oral regions drains directly into the general circulation.

Barrier to drug absorption from these routes is epithelium of oral mucosa.

In general, sublingual tablets are designed to dissolve slowly to minimize possibility of swallowing the dose.

Exception include: Nitroglycerin, Isosorbide dinitrate

tablets which dissolves within minutes in buccal cavity to provide prompt treatment of acute anginal episodes.

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FACTORS TO BE CONSIDERED:

Lipophilicity of drug: The lipid solubility should be high for absorption.

Salivary secretion: Drug should be soluble in buccal fluid.

pH of saliva: pH of saliva is usually 6.

Storage compartment: Some drugs have storage compartment in buccal mucosa. E.g., Buprenorphine

Thickness of oral epithelium: Sublingual absorption is faster than buccal, because former region is thinner than that of buccal mucosa

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FACTORS THAT LIMIT DRUG ADMINISTRATION

Limited mucosal surface area.Taste of medicament and discomfort. EXAMPLES: Nitroglycerin, Isosorbide dinitrate, Progesterone, Oxytocin, Fenosterol, Morphine.

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RECTAL ADMINISTRATION:Absorption across the rectal mucosa occurs by passive diffusion.

This route of administration is useful in children, old people and unconscious patients.

Eg., drugs that administered are: aspirin, acetaminophen, theophylline, indomethacin, promethazine & certain barbiturates.

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TOPICAL ADMINISTRATION:

MUCOSAL MEMBRANES (eye drops, antiseptic, sunscreen, nasal, etc.)

SKIN a. Dermal - rubbing in of oil or ointment (local action) b. Trandermal - absorption of drug through skin (systemic action) i. stable blood levels ii. no first pass metabolism iii. drug must be potent.

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Skin consist of three layers :EpidermisDermis Subcutaneous fat tissue

The main route for the penetration of the drugs is generally through epidermal layer

Stratum corneum is the rate limiting barrier in passive percutaneous absorption of drug.

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THREE PATHWAYS POSTULATED FOR THE DIFFUSION OF SOLUTES THROUGH THE SKIN:-

1. Transcellular (passive diffusion)2. Intercellular (Paracellular) The para cellular route involves the passes of molecules through inter cellular space while the trans cellular route involves transport into and across cell.

3. Transappendageal- drug diffusion through a) Hair follicles b) Sweat glands c) Sebaceous glands

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The stratum corneum is the outermost layer of the epidermis and is composed mainly of dead keratinized cells (from lack of oxygen and nutrients). It has a thickness between 10 - 40 μm.

The dermis is the layer of skin beneath the epidermis. It contains the hair follicles, sweat glands, sebaceous glands, apocrine glands, lymphatic vessels and blood vessels.

Hypodermis - Its purpose is to attach the skin to underlying bone and muscle as well as supplying it with blood vessels and nerves. The main cell types are fibroblasts, macrophages and adiposites (the hypodermis contains 50% of body fat).

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OCULAR ADMINISTRATIONEye is the most easily accessible site for topical administration of a medication.

Topical application of drug to eyes meant for :

Mydriasis, miosis, anesthesia, treatment of infection, glaucoma etc.

Ophthalmic solution are administered into cul-de-sac.

Barrier to intra occular penetration is cornea. It possess both hydrophilic and lipophilic characteristics.

pH of lachrymal fluid is 7.4.

pH of lachrymal fluid influences absorption of weak electrolyte like Pilocarpine.

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High pH of formulation: decrease tear flow and Low pH of formulation: increases tear flow.

Human eye can hold around 10 microlitre of fluid. So small volume in concentrated form increases effectiveness.

Viscosity imparters increases bioavailability e.g., oily solutions, ointment etc.

Systemic entry of drug occur by lachrymal duct which drains lachrymal fluid into nasal cavity.

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COMPOSITION OF EYE:-

Water - 98%

Solid -1.8%

Organic element – Protein - 0.67%, sugar - 0.65%, Nacl - 0.66%

Other mineral element sodium, potassium and ammonia - 0.79%

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INTRA NASAL ADMINISTRATIONDrugs generally administered by intra nasal route for treatment of local condition such as perennial rhinitis, allergic rhinitis and nasal decongestion etc.

Absorption of lipophilic drugs through nasal mucosa by passive diffusion and absorption of polar drugs by pore transport.

Rate of absorption of lipophilic drugs depend on their molecular weight.

Drugs with molecular weight less than 400 daltons exhibit higher rate of absorption.

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PARENTERAL ROUTES

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INTRAVENOUS ROUTEThis route is used when a rapid clinical response is required like treatment of epileptic seizures, acute asthmatic and cardiac arrhythmias.

There may also be a danger of precipitation of drug in the vein if the injection is too rapidly. This could result in thrombophlebitis.

This mode of administration is required with drugs having short half lives and narrow therapeutic index.

Bioavailability is not considered by this route.Mainly antibiotics are administered by this route.

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Intra arterial injectionIn this route the drugs are injected directly into the artery.

It is mainly used for cancer chemotherapy.

It increased drug delivery to the area supplied by the infused artery and decreased drug delivery to systemic circulation.

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INTRA MUSCULAR INJECTIONAbsorption of drug from muscles is rapid and absorption rate is perfusion rate limited.

Polypeptides of less than approx 5000 gram per mole primarily pass through capillary pathway.

Greater than about 20000 g/mol are less able to traverse capillary wall, they primarily enter blood via lymphatic pathway.

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SUBCUTANOUS ROUTE:

1. Slow and constant absorption 2. Absorption is limited by blood flow, affected if circulatory problems exist.3. The blood supply to this is poorer than that of muscular tissue.4. Concurrent administration of vasoconstrictor will slow

absorption, e.g. Epinephrine.5. The absorption is hastened by massage, application of heat to increase blood flow and inclusion of enzyme

Hyaluronidase in drug solution. eg. Insulin.

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PULMONARY ADMINISTRATION

The drugs may be administered for local action of bronchioles or their systemic effects through absorption of lungs.

Inhalation sprays and aerosols are used to deliver the drugs to the lungs.

Larger surface area of alveoli, high permeability of alveolar epithelium for drug penetration, and a rich vasculature are responsible for rapid absorption of drugs by this route

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In general particles greater than 10mm are retained in the throat and upper airways whereas fine particles reach the pulmonary epithelium

Drugs generally administered by this route are bronchodilators (e.g.. Salbutamol, isoproterenol), antiallergic (e.g.. Cromolym sodium), and antiinflammatory (e.g.. Betamethasone, dexamethasone).

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VAGINAL ADMINSTRATION:-Drugs meant for intra vaginal application are generally intended to act locally in the treatment of bacterial and fungal infections.

The route is now used for systemic delivery of contraceptives and other steroids, without the disadvantage of first-pass metabolism.

Controlled delivery and termination of drug action when desired is possible with this route.

Factors that influence absorption from intravaginal site include pH of lumen fluids, vaginal secretions and microorganisms present in vaginal lumen which metabolise the drug.

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ROUTESBUCCAL/SUBLINGUAL – passive diffusion, carrier mediated transportDrugs- nitrites and nitrates.RECTAL- passive diffusionDrugs- Aspirin, paracetamol.INTRAMUSCULAR- Passive diffusion, pore transportDrugs- Phenytoin and digoxin.SUBCUTANEOUS- passive diffusionDrugs- insulin, heparin.INTRANASAL- passive and pore transportDrugs- antihistamines.VAGINAL- passive diffusionDrugs- steroidal drugs and contraceptives.

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REFERENCES

1. Biopharmaceutics & pharmacokinetics by D.M Brahmankar & Sunil B. Jaiswal.2. Biopharmaceutics & pharmacokinetics by G.R.Chatwal.3.www.google.com.

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Thank you all