1

ABSORPTION OF DRUGS THROUGH NON-ORAL

ROUTES

CONTENTS:-• Introduction• Routes of administration• Enteral routes• Parenteral routes• Topical routes• Comparison of different routes• References

2

INTRODUCTION:-• DEFINITION- “The process of

movement of unchanged drug from the site of administration to systemic circulation is called as drug absorption”.

3

• ORAL ROUTE:- It is the most common route of drug administration.

Drug is given through oral cavity. Dosage forms- Capsules, powder, Tablets, Syrup,

emulsion, Suspension, elixirs etc.

4

ADVANTAGES:-• Safe • Convenient• Self- administered• Pain free• Easy to take• Economical• Good absorption• No need for sterilization

DISADVANTAGES:-• Slow absorption, slow action• Irritable and unpalatable

drugs- nausea and vomiting• First-pass effect- Due to

Biotransformation• Food–Drug interactions and

Drug-Drug interactions

5

ROUTES OF ADMINISTRATION:-

ENTERAL ROUTE

• Oral• Sublingual/buccal• Rectal

PARENTERAL ROUTE

• I.V• I.M• SC• ID, IA, IP, IT

TOPICAL ROUTE

• Transdermal• Inhalation • Intranasal• Intraoccular• Intravaginal 6

I. ENTERAL ROUTE:-A. BUCCAL/SUBLINGUAL ROUTE:- The two sites for

oral mucosal delivery of drugs are:Sublingual route- the drug is placed under the

tongue and allowed to dissolve.Buccal route- the medicament is placed between

the cheek and the gum.

7

Passive diffusion is the major mechanism for absorption of most drugs; nutrients may be absorbed by career-mediated processes.

Examples-oAnti anginals- nitrites and nitrates e.g.; nitro-

glycerine spray (translingual)oAnti hypertensives- nifedipineoAnalgesics- morphine; bronchodilators- fenoteroloSteroids- oestradiol oPeptides- oxytocin

8

Advantages-Rapid absorption and higher blood levels No first pass metabolismNo degradation of drugs such as that encountered in

the GITPresence of saliva facilitates both drug dissolution and

permeation.

DISADVANTAGES:-Concern for taste and discomfortLimited mucosal surface- small doses are administered.

9

B. RECTAL ROUTE:- Drugs may be administered as solutions (micro-

enemas) or suppositories. In this form, a drug is mixed with a waxy substance

that dissolves or liquefies after it is inserted into the rectum.

The drug is absorbed from the rectum and anal canal by passive diffusion of the unionized drug.

EXAMPLES: Aspirin, Paracetamol, theophylline, few barbiturates, etc.

10

Advantages-Alternative route for administration of unpleasant

drugs Avoids nausea, vomitingCan be used in case of unconscious patientsBypasses presystemic hepatic metabolism from

lower half of rectum.

Disadvantages-Absorption is sometimes irregular and incomplete

and many drugs cause irritation of rectal mucosa. 11

II. PARENTERAL ROUTE:-Direct delivery of drug in to systemic circulation without intestinal mucosaIntradermal (I.D.) (into skin)Subcutaneous (S.C.) (into subcutaneous tissue)Intramuscular (I.M.) (into skeletal muscle)Intravenous (I.V.) (into veins)Intra-arterial (I.A.) (into arteries)Intra-thecal (I.T.) (cerebrospinal fluid)Intra-peritoneal (I.P.) (peritoneal cavity)Intra - articular (Synovial fluids) 12

13

A. INTRAVENOUS INJECTIONS (IV):- It is used to introduce drug directly into the systemic circulation. Intravenous drip or infusion pump is used. Catheters can also be used.

14

Advantages-For drugs that are not

absorbed orally.Avoids first-pass

metabolism Rapid effect Large quantities can be

given100% bioavailability-

Absorption phase is bypassed.

Disadvantages-Cannot be recalled by

strategies such as emesis or by binding to activated charcoal.

Induce haemolysis or other adverse reactions.

Thrombophlebitis of vein and necrosis of adjoining tissue.

Suspensions may block the capillaries. 15

B. INTRAMUSCULAR ROUTE:- Introduces drug in muscles. Thus compared to IV,

the absorption is slower and incomplete. Absorption of lipophilic drugs occurs by passive

diffusion into blood circulation and lymphatic system.

Hydrophilic and ionic drugs are absorbed into blood circulation via the capillary pores.

16

ADVANTAGES- Oily suspensions for

depot and slow release preparations.

For drugs which degrade after oral route- insulin

Rapid onset of action.Mild irritants can be

given.

DISADVANTAGES-Metabolism of drugs in

muscle tissues.Precipitation of drug at

the injection site.Irritating drugs may be

very painful.

17

C. SUBCUTANEOUS ROUTE:-It is used only when drug does not cause irritation, otherwise

severe pain, necrosis or tissue damage may occur. Isotonic solutions are injected to reduce pain and can be

utilised for sustained effect.Incorporation of vasoconstrictor substance will retard the

absorption.Massage, exercise, application of heat or inclusion of

vasodilator will increase the absorption.

18

ADVANTAGES-Rapid onset of action due to rapid access to

circulation.Pain not occurs when patch is used.Used for vaccines and drugs not absorbed orally, e.g.

insulin.

DISADVANTAGES-Slower absorption when compared to IM.Rate of absorption depends upon blood flow and

injection volume. 19

D. INTRA-PERITONEAL (IP):- It is most widely used in laboratory animals.

The drugs can be directly administered into the subarachnoid space and thus the effects will be localised to the spinal nerves and meninges.

E.g. In spinal anaesthesia or CNS infections like tuberculosis, meningitis in which streptomycin can be given intrathecally.

20

E. INTRA-ARTERIAL (IA):- it is only limited for the administration of radio-opaque media for diagnostic purposes or to localize the effect of drug to a particular tissue or organ by injecting the drug into the hepatic artery (Incase of hepatic tumours).

Most widely used for experimental work.E.g. treatment of liver tumours and head/neck

cancers.

21

F. INTRA-DERMAL (ID):- drug is given within skin layers (dermis), thus painful.

Mainly used for testing sensitivity to drugs.E.g. penicillin, ATS (anti tetanus serum),

administration of vaccine (like small pox vaccine).

G. INTRA-ARTICULAR:- injections of antibiotics and corticosteroids are administered in inflamed joined cavities by experts.

E.g. hydrocortisone in rheumatoid arthritis.

22

III. TOPICAL ADMINISTRATION:-• There are three pathways postulated for the

diffusion of solutes through the skin:Transcellular (passive diffusion)Intercellular (paracellular)Transappendageal– drug diffusion through: Hair follicles Sweat glands, and Sebaceous glands.

23

• Diffusion through the multiple lipid bilayers of dead, hydrophilic keratinized and horny cells of stratum corneum is the rate limiting step. • Lipophilic drugs show penetration through this layer

i.e., intercellular route.• Hydrophilic keratinized cells allows intracellular

penetration of polar drugs. • Dosage forms here are cream, ointments, lotion,

gels, transdermal patches and disks.

24

Includes administration of drugs to any mucous membrane like:

i. Skin (percutaneous) e.g. allergy testing, topical local anaesthesia

ii. Mucous membrane of respiratory tract (Inhalation) e.g. asthma

iii. Eye drops e.g. conjunctivitisiv. Ear drops e.g. otitis externav. Intranasal, e.g. decongestant nasal spray

25

A. TRANSDERMAL DRUG DELIVERY:-Drug in solution or bound to a polymer is held in

reservoir between occlusive backing film and rate controlling micropore membrane, under surface of which is smeared with an adhesive.

Site of application includes upper arm, chest, abdomen, etc.

26

Advantages-Protects drug from GI

environment and first pass metabolism.

Increased patient compliance.

Provides constant plasma drug profile.

Easy to terminate drug therapy by removing patch.

Disadvantages-Toxic skin reactions.Variable blood flow to

skin.Complex relationship

between drug, vehicle, skin physiology.

27

Ionic drugs can be absorbed by novel techniques such as:

a. Iontophoresis- An ionised drug solution is placed on the skin and application of current will drive charged drug molecules away from electrodes and into the tissues; and vice versa.

E.g. cortisol, lidocaine, proteins and peptides.b. Phonophoresis- it is defined as the movement of

drug molecules through skin under the influence of ultrasound.

28

B. INTRANASAL ADMINISTRATION:- drug absorption by this route is as rapid as parenteral administered because of its high permeability and rich vasculature.

Examples:• Drugs used to treat local symptoms like nasal

congestion, rhinitis, etc.

29

Mechanisms for the drug delivery from nose to the brain:• Drug that reaches the blood circulation may

subsequently cross the blood-brain barrier.• Substances may cross the olfactory epithelium via

simple diffusion, receptor mediated transcytosis or paracellular transport. The substance may then follow the nerve to the CNS.

30

ADVANTAGES-Lipophilic drugs shows rapid absorption by diffusion.By use of permeation enhancers, even a drug upto

6000 Daltons shows reasonable bioavailability.Polar drugs are absorbed by pore transport.

DISADVANTAGES-Permeation of drugs is influenced by pH of nasal

secretions (5.5 to 6.5), viscosity. Pathological conditions such as common cold.

31

C. VAGINAL ADMINISTRATION: - drugs meant for intravaginal action are generally intended to act locally in the treatment of bacterial or fungal infections or prevent conception.

The drugs are absorbed by passive diffusion into the systemic circulation.

E.g. contraceptives and other steroids.

32

ADVANTAGES- Avoids first pass

metabolism.Controlled delivery and

termination of drug action when desired.

DISADVANTAGES-Drug absorption may be

influenced by pH of lumen fluids (4 to 5), vaginal secretions and microorganisms present in the vaginal lumen which may metabolise the drug.

33

D. INTRA-OCCULAR ADMINISTRATION: -Sterile aqueous solutions of drugs are administered

in the conjunctival cul-de-sac. Like skin, cornea is the composed of lipoidal and

aqueous layers. The epithelial and endothelial cells are lipoidal and stroma is acellular with high water content.

The unionized drug easily penetrate epithelial and endothelial, the former serves as depot for lipophilic molecules.

34

ADVANTAGES:-Provide prolonged duration of action.Side effect from such systems are very low.

DISADVANTAGES:-Proteins present in tears bind with drugs and

such bound drugs due to bulkiness are difficult to absorb.

35

E. PULMONARY ADMINISTRATION:-• Alveolar epithelium and the capillary

endothelium have high permeability to hydrophilic as well as lipophilic substances.• Absorption of hydrophilic drugs occur by

diffusion through aqueous membrane pores and is inversely proportional to the molecular size of the drug.• Lipophilic drugs are absorbed by passive

diffusion.36

• E.g. Gaseous or volatile anaesthetics, Inhalation of amyl nitrate to abort angina attacks.

37

Drug delivery to lungs is dependent upon the particle size of the aerosolised droplets-• Particles > 10µ impact on the mouth, throat or

upper respiratory tract mucosa and do not reach the pulmonary tree.• Very small particles- 0.6 µ from which drug

absorption is rapid.• Particles 1-5µ deposit within the lower

respiratory tract.

38

ADVANTAGES-• Rapid absorption.• Avoids first –pass hepatic metabolism.• Produce rapid action with reduced systemic side

effects.DISADVANTAGES-• Drug may be metabolized in the bronchial wall and

the lung. • Limited for the administration of drugs that affect

pulmonary system like bronchodilators (salbutamol), anti-allergics (cromolyn).

39

Comparison of different routes:-ROUTE/ONSET OF ACTION

ABSORPTION MECHANISM

EXAMPLES

Buccal/Sublingual(3-5mins)

Passive diffusion, carrier mediated transport

Nitrites and nitrates- antianginals, nifedipine, morphine, etc.

Rectal (5-30mins)

Passive diffusion Aspirin, paracetamol, theophylline, etc.

Transdermal (minutes-hours)

Passive diffusion Nitroglycerine, lidocaine, scopolamine, testosterone, etc.

Subcutaneous (15-30mins)

Passive diffusion Insulin, heparin, C.R, implants. 40

ROUTE/ ONSET OF ACTION

ABSORPTION MECHANISM

EXAMPLES

Inhalation (2-3mins)

Passive diffusion, pore transport

Salbutamol, cromolyn, Beclomethasone

Intramuscular (10-20mins)

Passive diffusion, endocytosis, pore transport

Phenytoin, digoxin, steroids and antibiotics, etc.

Intranasal (3-5mins)

Passive diffusion, pore transport

Phenylpropylamine, antihistamines

Intraocular Passive diffusion Atropine, pilocarpine, adrenaline, etc.

Vaginal Passive diffusion Steroids, contraceptives, metronidazole, etc.

41

REFERENCES:-1. Milo Gibaldi; Biopharmaceutics and Clinical

Pharmacokinetics; PBS Publishers; 4th Edition, 2005; Page No: 80-118.

2. J.S.Kulkarni, A.P.Pawar, V.P. Shedbalkar; Biopharmaceutics and Pharmacokinetics; CBS Publishers and Distributors; 1st Edition; 2006; Page No: 47-59.

3. CVS Subramanyam, Biopharmaceutics and Pharmacokinetics-concepts and applications, Vallabh Prakashan Publishers, 1st Edition, 2010, Page No: 115-128.

4. D.M.Brahmankar, Sunil B.Jaiswal; Biopharmaceutics and Pharmacokinetics-A Treatise; Vallabh Prakashan Publishers; 1st Edition; 1995; Page No: 81-92.

42

THANK YOU..!!

43