ABSORPTION OF DRUG FROM NON-PER ORAL ROUTES

BY M.V. UMA MAHESHWARI DEPARTMENT OF PHARMACEUTICS

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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 Click to edit Master subtitle style such sites is a lipoidal membrane similar to the GI barrier . The major mechanism in the absorption is passive diffusion.
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Mucosal delivery
Ocular delivery
Nasolacrimal drainage system

Oral delivery
G-I absorption

Presystemic elimination Liver

Nose Nasal Delivery

Nasal epithelium

Pulmonary Delivery Buccal, sublingual gingival

Respirator y membrane Oral mucosa Rectal mucosa

Systemic circulation

Rectal delivery (lower half) Vaginal Vaginal mucosa delivery 5/1/12

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SUBLINGUAL / BUCCAL ROUTE

SUBLINGUAL 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. Click to edit Master subtitle style 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

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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.

aspirin, acetaminophen, theophylline, indomethacin, promethazine & certain 5/1/12

Eg., drugs that administered are:

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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 : Epidermis Dermis 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 m.
Click to edit Master subtitle style skin beneath The dermis is the layer of

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 5/1/12 1414

OCULAR ADMINISTRATION

Eye 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 edit Master subtitle style Click to 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 administration Drugs 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 editpassive diffusionstyle absorption of Click to by Master subtitle and 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 ROUTE
This 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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In this route the drugs are injected directly into the artery.
Click mainly Master subtitle style It is to edit used for cancer chemotherapy.

Intra arterial injection

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 INJECTION

Absorption 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. 5/1/12 2525 eg. Insulin.

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 Master subtitle style delivery of Click to edit now used for systemic 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 5/1/12 2929 and microorganisms present in vaginal lumen

ROUTES
BUCCAL/SUBLINGUAL passive diffusion, carrier mediated transport Drugs- nitrites and nitrates. RECTAL- passive diffusion Drugs- Aspirin, paracetamol. INTRAMUSCULAR- Passive diffusion, pore transport Drugs- Phenytoin and digoxin. SUBCUTANEOUS- passive diffusion Drugs- insulin, heparin. INTRANASAL- passive and pore transport Drugs- antihistamines. VAGINAL- passive diffusion Drugs- steroidal drugs and contraceptives. 5/1/12 3030

REFERENCES
1. Biopharmaceutics & pharmacokinetics by D.M 5/1/12

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Thank you all

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