A SEMINAR ON

INTRA-NASAL DRUG DELIVERY SYSTEM

BY: NALEEN RAJ BHANDARI B-PHARM (2/4) MAHESHWARA INSTITUTE OF PHARMACY

CONTENTS
INTRODUCTION ADVANTAGES FUNDAMENTAL FACTORS MECHANISMS AND PATHWAYS DELIVERY SYSTEMS ENHANCEMENT IN ABSORPTION APPLICATIONS EXAMPLES CONCLUSIONS REFERENCES

INTRODUCTION
In ancient times the Indian Ayurvedic system of medicines used nasal route for administration of drug and the process is called as Nasya It has been used for local effects extensively in decongestant and local activity. But, in recent times intranasal drug delivery is being considered as a preferred route of drug delivery for systemic bioavailability Various proteins & peptides have shown a good bioavailability

Intranasal Drug Delivery System: Advantages

Its easy and convenient Can be easily administered to the unconscious patients

Compared to oral medications, intranasal medication delivery results in:

Faster delivery to the blood stream and higher blood levels No destruction by stomach acid and intestinal enzymes No destruction by hepatic first pass metabolism

Compared to IV medications, intranasal medication delivery results in:

Comparable blood levels depending on the drug and dose.

Fundamental Factors Affecting Nasal Absorption

Molecular weight: Absorption of drugs decreases as the
molecular weight of drug molecules increases. Mc Martin et al reported a sharp decline in drug absorption having molecular weight greater than 1000Dalton

Lipophilicity Drug concentration: Absorption increases as

concentration of drug increases. 1-tyrosine shows increased absorption at high concentration in rate..

Particle size:

Particle size 10-50 microns adheres best to the nasal mucosa.

MECHANISMS

Two mechanisms are found to be involved:

Fast rate mechanism, which is lipophilicity dependent. Slow rate mechanism, which is dependent on molecular weight. Ex: Nasal delivery of insulin, manitol follows a transport mechanism involving passive diffusion While, absorption of water soluble molecules like sodium cromoglycate take place by diffussion through aqueous pores

PATHWAYS

Possible drug absorption pathways

DELIVERY SYSTEMS
Various delivery systems are used like
Nasal spray Nose drops Aerosol spray Metered dose nebulizer Saturated cotton pledget The insufflators Mucosal atomizer device (M.A.D) Microspheres

ENHANCEMENT IN ABSORPTION
Use of absorption enhancers Increase in residence time Administration of drugs in the form of microspheres Various enhancers used Surfactants Phospholipids Chelaters Glycols Cyclodextrins Capable of increasing membrane fluidity and leaching of proteins and lipids from the membrane

Applications of Intranasal Drug Delivery

Nasal Delivery of Organic based Pharmaceuticals
e.g.: Progesterone, Estradiol, Testosterone, Hydralzine, Propranolal, Cocain, Naloxon & Nitrogylcerine. These have shown good Bioavailability by this route. Water-soluble organic based compounds such as Sodium cromoglycate were also found to be well absorbed.

Nasal Delivery of Peptide-Based Drugs

As peptide based drugs are susceptible to hepatogastrointestinal first pass elimination & instability, they show very low oral bioavailability thus administered through nasal route.

EXAMPLES SHOWING DIFFERENT DELIVERY SYSTEMS

TRADITIONAL & KURVES DELIVERY

MUCOSAL AUTOMIZATION DEVICE (M.A.D)

EXAMPLES

Accuspray from BD Medical Pharmaceutical Systems is a singleuse nasal sprayer for monodose or bidose administration

INTRANASAL Naloxone

Conclusions
NDDS provides route of drug administration for drugs, which degrade due to first pass metabolism Though it also poses many challenges such as low absorption, toxicological problems, high dose requirements etc.,, thus use of absorption enhancers is proving to be useful increasing the absorption. Insulin is being extensively investigated for its nasal absorption, which may prove a major turnaround in diabetics treatment. With ongoing efforts to improve bioavailability of protein and peptide drug through nasal route, the nasal route can become the prime route for administration of protein drugs..

REFERENCES
Shaji J and Marathe S.W. NASAL DRUG DELIVERY SYSTEM: OPPORTUNITIES & CHALLENGES INDIAN DRUGS Vol. 45 No. 5 May 2008 Pg no (345 353)