In ancient time, Indian Ayurvedic system of

medicine used nasal route for administration

of drug, called “Nasya”.

It has been an accepted form of treatment in

Ayurvedic system of Indian medicine.

Certain drugs are unsuitable for oral

administration.

Parenteral route is also an inconvenient route for

long term therapy due to the potential side

effects.

Psychotropic substances and hallucinogens have

been used in the form of snuffs.

Many drugs have better BA by the nasal route

than by oral route.

This is attributed to a rich vasculature and a

highly permeable structure of the nasal mucosa.

Avoids hepatic first pass metabolism, gut wall metabolism.

Non- invasive route of administration.

Convenient and easily accessible.

Absorption will be faster producing rapid effect and better BA.

Drugs with poor oral bioavailability are suitable candidates.

Nasal pathology

Absorption enhancers used in nasal drug delivery system may cause toxicity

Nasal cavity provides smaller absorption surface area when compared to GIT

Immunological reaction

Rapid mucociliary clearance

A - superior turbinate B - middle turbinateC - inferior turbinateD - vestibuleE - nasopharynxDotted areas - the olfactory region

Nasal passage, which runs from the nasal vestibule, to the nasopharynx

Nasopharynx depth 12-14cms

Lining is ciliated, highly vascular, rich in mucous glands and goblet cells

Cilium-5μm in length & 0.2 μm in diameter and moves @20beats/sec

Normal pH in the range of 5.5- 6.5 and contain a variety of enzymes.

1. Nasal vestibule and Ostium

2. Nasal turbinates

3. Mucus and cilia

4. Olfactory region

The rate of diffusion and rate of clearance from the nasal cavity is influenced by:

1. The physicochemical properties of the formulation vehicle.

2. The particle size.

3. Surface charge of a drug.

4. Any additives incorporated.

1. Effect of molecular size:Nasal absorption decreases for drugs with molecular weight > 1000 dalton.

2. Effect of perfusion rate:Eg: PhenobarbitolAs the perfusion rate increases, nasal absorption first increases and then reaches a plateau level, independent of the rate of perfusion.

3. Effect of solution pH:The effect of the pH of a perfusion solution on nasal absorption was examined using a water soluble ionisable compound such as benzoic acid in the pH range 2 - 7.1

4. Effect of drug concentration:Eg: Monitoring the disappearance of 1-tyrosyl 1-tyrosine and the formation of 1-tyrosine.The nasal absorption of 1-tyrosine depends upon its concentration.

This was investigated using SS-6, an octapeptideand horseradish peroxidase, a protein molecule.

Two mechanisms of transport are involved:1. Transcellular – Across the cell2. Paracellular – Between the cell

Aqueous route of transport

This route is slow and passive

There is an inverse correlation between intranasal absorption and the molecular weight of water-soluble compounds

Good systemic BA can be achieved for molecules with a molecular wt of up to 1000 daltons with enhancer

Transport through a lipoidal route

Responsible for the transport of lipophilic drugs that show a rate dependency on their lipophilicity.

Drug also cross cell membranes by an active transport route via carrier-mediated means or through the opening of tight junctions.

Eg: Chitosan

Enhancement in Absorption:To modify the physicochemical properties of a drug.

Salt or ester formation: Has better trans-nasal permeability

Formulation design: Proper selection of formulation excipients could enhance the nasal absorption of drugs.

Surfactants:Incorporation of surfactants could modify the permeability of nasal mucosa.

1. Metered dose nebulizer2. Mucoadhesive powder sprays3. Sustained release formulations4. Nasal sprays 5. Nasal drops6. The saturated cotton pledget7. The insufflator

Operates by mechanical actuation.

Delivers a predetermined volume with precision Eg: Corticosteroids, Tramazoline and nasal decongestant.

They have also been explored as the NDDS for the systemically –active drugs

Used for the delivery of insulin

Produces a drug absorption that is more effective and less irritating than liquid forms.

In the nasal cavity, the powder absorbs nasal fluid and becomes swollen

For the mucoadhesive powder spray,The powder mixture was prepared with HPC and was administered by a special applicator called ‘Pulizer’.

The advantages of using HPC:1) drug dose may be reduced.2) side effects may be lowered.3) longer duration of effect is expected.

They do not give reproducible dosing.

They deposit at their impaction site, in the anterior, unciliated regions of the nasal cavity.

Thus leads to slow transport of the moiety along the surface.

Rely upon the instillation of one or more drops of drug solution into the nasal cavity.

Nasal drops if administered correctly, deposit drug throughout the nasal cavity

Clearance of the drops is faster than spray

1) In vivo nasal absorption model2) Ex vivo nasal perfusion model.

1) In-vivo nasal absorption model:Animal models used are:a)Rat modelb)Rabbit modelc)Dog modeld)Sheep modele)Monkey model.

An incision is made in the neck and the trachea is cannulated.

Another tube is inserted through the esophagustowards the posterior part of the nasal cavity.

Drug solution is delivered to the nasal cavity. Blood samples are collected from the femoral vein Gives an idea of the drug absorbed through the

nasal mucosa.

A funnel is provided underneath the nose to lead the drug solution into the drug reservoir.

Reservoir solution is circulated through the nasal cavity of the rat.

Perfusion solution passes out from the nostril and flows into the drug reservoir soln again.

Novel drug delivery system- By Yie.W.Chein,Page no-229-265.

Targeted and controlled drug delivery systems-By S.P.Vyas and R.K.Khar, Page no-315-382.

Drug Delivery Systems by Kewal K. Jain, Pg 9-10.