Nasal Drug Delivery System

In ancient times the Indian Ayurvedic system of medicines used nasal route for administration of drug & the process is called “Nasya”.
Intranasal drug delivery is now recognized to be a useful and reliable alternative to oral and parenteral routes. Undoubtedly, the intranasal administration of medicines for the symptomatic relief and prevention or treatment of topical nasal conditions has been widely used for a long period of time.
However, recently, the nasal mucosa has seriously emerged as a therapeutically viable route for systemic drug delivery.
In general, among the primary targets for intranasal administration are pharmacologically active compounds with poor stability in gastrointestinal fluids, poor intestinal absorption and/or extensive hepatic first-pass elimination, such as peptides, proteins, and polar drugs. The nasal delivery seems to be a favorable way to circumvent the obstacles for the blood-brain barrier (BBB) allowing the direct drug delivery in the biophase of the central nervous system (CNS)-active compounds. It has also been considered to the administration of vaccines.

Advantages of Nasal Drug Delivery System

1. Hepatic first-pass metabolism avoided.
2. Rapid drug absorption and quick onset of action.
3. The bioavailability of larger drug molecules can be improved by means of an absorption enhancer.
4. Bioavailability for smaller drug molecules is good.
5. Convenient for long term therapy, compared to parenteral medication.
6. Drugs possessing poor stability G.I.T fluids given by nasal route.
7. Easy and convenient.
8. Easily administered to unconscious patients.

Disadvantages of Nasal Drug Delivery System

1. Pathologic conditions such as cold or allergies may alter significantly the nasal bioavailability.
2. The histological toxicity of absorption enhancers used in the nasal drug delivery system is not yet clearly established.
3. Relatively inconvenient to patients when compared to oral delivery systems since there is a possibility of nasal irritation.
5. The nasal cavity provides a smaller absorption surface area when compared to GIT.

Anatomy and physiology of Nasal Cavity

a) The nasal cavity consists of three main regions:
1) Nasal vestibule
2) Respiratory region
i) Major drug absorption.
ii) 15-20 % of the respiratory cells covered by a layer of long cilia size 2-4 μm.
3) Olfactory region
A small area in the roof of the nasal cavity of about 10 cm2 drug is exposed to neurons thus facilitate it across the cerebrospinal fluid.
b) The normal pH of the nasal secretions in an adult is 5.5-6.5.
c) Infants and young children are 5.0-6.7.
d) The nasal cavity is covered with a mucous membrane. Mucus secretion is composed of 95% water, 2%-mucin, 1%-salts,1%-of other proteins such as albumin, lysozyme and lactoferrin and 1%-lipids.

Mechanism of Drug Absorption

Paracellular (intercellular) Slow and passive absorption of peptides and proteins associated with intercellular spaces and tight junctions.
Transcellular: Transport of lipophilic drugs passive diffusion/active transport.
Transcytotic: Particle is taken into a vesicle and transferred to the cell.

FORMULATION APPROACHES

1. Nasal gels
2. Nasal Drops
3. Nasal sprays
4. Nasal Powder
5. Liposome
6. Microspheres

Nasal Gels

High-viscosity thickened solutions or suspensions.

Advantages:

1. Reduction of post-nasal drip due to high viscosity
2. Reduction of taste impact due to reduced swallowing
3. Reduction of anterior leakage of the formulation

Nasal Drops

Nasal drops are one of the most simple and convenient systems developed for nasal delivery. The main disadvantage of this system is the lack of dose precision and therefore nasal drops may not be suitable for prescription products. It has been reported that nasal Drops deposit human serum albumin in the nostrils more efficiently than nasal sprays.

Nasal sprays

Both solution and suspension formulations can be formulated into nasal sprays. Due to the availability of metered-dose pumps and actuators, a nasal spray can deliver an exact dose from 25to200μm. The particle size and morphology (for suspensions) of the drug and viscosity of the formulation determine the choice of pump and actuator assembly.

Nasal Powder

This dosage form may be developed if solution and suspension dosage forms cannot be developed e.g., due to lack of drug stability. The advantages to the nasal powder dosage form are the absence of preservative and superior stability of the formulation. However, the suitability of the powder formulation Is dependent on the solubility, particle size, aerodynamic properties and nasal irritancy of the active drug and/or excipients. Local application of the drug is another advantage of this system.

Liposomes

Liposomal Nasal solutions can be formulated as drugs alone or in combination with pharmaceutically acceptable excipients. Administered to the respiratory tract as an aerosol or solution for a nebulizer, or as a micro-fine powder for insufflation, alone or in combination with an inert carrier such as lactose, the particles of the formulation have diameters of less than 50 microns.

Microspheres

Specialized systems becoming popular for designing nasal products, as it provides prolonged contact with the nasal mucosa. Microspheres (in the powder form) swell in contact with nasal mucosa to form a gel and control the rate of clearance from the nasal cavity. Thus increases the absorption and bioavailability by adhering to the nasal mucosa and increase the nasal residence time of the drug. The ideal microsphere particle size requirement for nasal delivery should range from 10 to 50 μm as smaller particles.

RECENT ADVANCES

1. Currently, the majority of intranasal products on the market are targeted toward local relief or the prevention of nasal symptoms. The trend toward the development of intranasal products for systemic absorption should rise considerably over the next several years. The development of these products will be in a wide variety of therapeutic areas from pain management to treatment for erectile dysfunction.
2. However, the primary focus of intranasal administration, correlated with increasing molecular scientific knowledge and methods, will be the development of peptides, proteins, recombinant products, and vaccines. The nasal cavity provides an ideal administration site for these agents because of its accessibility, avoidance of hepatic first-pass metabolism, and large vascular supply.
3. Future technologies in the intranasal arena will be concentrated on improved methods for safe, efficient delivery systems primarily for molecular agents, but also for numerous therapeutic categories.
Related: Transdermal Drug Delivery System