Nasal Sprays - (Naso - Pulmonary Drug Delivery Systems)

Nasal Sprays

(Naso - Pulmonary Drug Delivery Systems)

Intended learning outcomes

At the end of the session students will be able to:

1.       Justify the need for nasal sprays, differentiate nasal sprays with other nasopulmonary devices

2.       Enlist the advantages and limitations of nasal sprays

3.       Describe formulation  aspects of nasal sprays

4.       Recall marketed formulations of nasal sprays

Nasal Sprays

• Intranasal drug delivery is recognized to be a useful and reliable alternative to oral and parenteral routes.

• The nasal route of drug delivery can be used for both local and systemic drug delivery. For instance, localized nasal drug delivery is usually used to treat conditions related to the nasal cavity, such as congestion, rhinitis, sinusitis and related allergic conditions.

• A diverse range of drugs including corticosteroids, anti-histamines, anti-cholinergic and vasoconstrictors can be administered locally. In recent years, achieving a systemic drug action using the nose as the entry portal into the body has received more attention.

• Also, the nasal delivery seems to be a favorable way to circumvent the obstacles for bloodbrain barrier (BBB) allowing the direct drug delivery in the biophase of central nervous system (CNS)-active compounds.

• It has also been considered to the administration of vaccines.

• Now a day’s multiple types of formulation are used to administer drug by nasal rout, which includes nasal spray, nasal drop, nasal powder, nasal gels & nasal insert etc.

• Administration of drugs through the nose in the spray dosage form is a noninvasive method that gives rapid onset of drug action. Because the nasals spray dosage form is cost-effective, easy to use/carry and self-administrable, it has high patient compliance.

• Therefore, nasal drug delivery has become a popular route of drug administration and has strong growth opportunity

Advantages of Nasal Drug Delivery System

1. Intranasal administration offers several practical advantages from the viewpoint of patients (non-invasiveness, essentially painless, ease drug delivery and favorable tolerability profile)

2. Rapid drug absorption.

3. Quick onset of action.

4. Hepatic first – pass metabolism is absent.

5. The bioavailability of larger drug molecules can be improved by means of absorption enhancer or other approach.

6. Better nasal bioavailability for smaller drug molecules.


1. Dose is limited because of relatively small area available for the absorption of drug.

2. Time available for drug absorption is limited.

3. Diseased condition of nose impairs drug absorption.

4. The absorption enhancers used to improve nasal drug delivery system may have histological toxicity which is not yet clearly established.

5. Absorption surface area is less when compared to GIT.

6. Nasal irritation

7. Certain surfactants used as chemical enhancers may disrupt and even dissolve Membrane in high concentration

Formulation of Nasal Sprays

• Nasal spray drug products contain therapeutically active ingredients (drug substances) dissolved or suspended in solutions or mixtures of excipients (e.g., preservatives, viscosity modifiers, emulsifiers, buffering agents) in nonpressurized dispensers that deliver a spray containing a metered dose of the active ingredient.

• The dose can be metered by the spray pump.

• A nasal spray unit can be designed for unit dosing or can discharge up to several hundred metered sprays of formulation containing the drug substance.

• Energy is required for dispersion of the formulation as a spray.

• This is typically accomplished by forcing the formulation through the nasal actuator and its orifice.

• The formulation and the container closure system (container, closure, pump, and any protective packaging) collectively constitute the drug product.

• The design of the container closure system affects the dosing performance of the drug product.

• Both solution and suspension formulations can be formulated into nasal sprays.

1) Active Pharmaceutical Ingredient

An ideal nasal drug candidate should possess the following attributes:

• Appropriate aqueous solubility to provide the desired dose in a 25–150 ml volume of formulation.

• Appropriate nasal absorption properties.

• No nasal irritation from the drug.

• A suitable clinical rationale for nasal dosage forms, e.g. rapid onset of action.

• Low dose. Generally, below 25 mg per dose.

• No toxic nasal metabolites.

• No offensive odors/aroma associated with the drug.

• Suitable stability characteristics.

2) Excipients used in nasal spray formulations

There are various types of excipients used in nasal formulations. Commonly used and frequently added excipients are as follows:

a) Buffers:

Nasal secretions may alter the pH of the administrated dose which can affect the concentration of un-ionized drug available for absorption.

Therefore, an adequate formulation buffer capacity may be required to maintain the pH in-situ.

Examples of buffer used in nasal spray sodium phosphate, Sodium citrate, citric acid.

b) Solubilizers:

Aqueous solubility of drug is always a limitation for nasal drug delivery in solution.

Conventional solvents or co-solvents such as glycols, small quantities of alcohol, Transcutol (diethylene glycol monoethyl ether), medium chain glycerides and Labrasol (saturated polyglycolyzed C8- C10 glyceride) can be used to enhance the solubility of drugs.

Other compounds can be used like, the use of surfactants or cyclodextrins such as HP–s Cyclodextrin that serve as a biocompatible solubilizer and stabilizer in combination with lipophilic absorption enhancers.

In these cases, their impact on nasal irritancy should be considered.

c) Preservatives:

Most nasal formulations are aqueous based so needs preservatives to prevent microbial growth.

Parabens, phenyl ethyl alcohol, benzalkonium chloride, EDTA and benzoyl alcohol are some of the commonly used preservatives in nasal formulations

d) Antioxidants:

A small quantity of antioxidants may be required to prevent drug oxidation. Commonly used antioxidants are sodium bisulfite, butylated hydroxytoluene, sodium metabisulfite and tocopherol.

Usually, antioxidants do not affect drug absorption or cause nasal irritation.

e) Humectants

Because of allergic and chronic diseases there can be crusts and drying of mucous membrane.

Certain preservatives/ antioxidants are also likely to cause nasal irritation especially when used in higher quantities.

Adequate intranasal moisture is essential for preventing dehydration. Therefore, humectants can be added especially in gel-based nasal products.

 Humectants avoid nasal irritation and do not affect drug absorption.

Common examples include glycerin, sorbitol and mannitol

f) Surfactants

Surfactant incorporation into nasal dosage forms can modify the permeability of nasal membranes, which may facilitate the nasal absorption of drug.

It also increase stability of suspension.

Common examples include Polysorbates.

g) Bioadhesive polymers

 Compound that is capable of interacting with biological material through interfacial forces and being retained on such material for prolonged periods of time is called as bioadhesive polymer. They are also called as mucoadhesive if biological material is mucus membrane.

The bioadhesive force of a polymer material is dependent on the nature of the polymer, the surrounding medium (pH), swelling and physiological factors (mucin turnover, disease state).

From a safety (nasal irritancy) point of view use of a combination of carriers is often recommended.

h) Penetration enhancer

Chemical penetration enhancers are widely used in the nasal drug delivery.






Isotonicity adjustment

Used to adjust the tonicity of the formulation

Sodium chloride, Dextrose


pH adjustment

Used to adjust pH same to physiological conditions and maximize drug stability

Sodium hydroxide, hydrochloric acid sulphuric acid



Purging used to reduce oxidation



Antimicrobial preservative

To avoid the microbial growth in the formulation

Benzalkonium chloride, ethanol, propylene glycol, Beczoyl Alcohol, chlorobutanol, Methyl paraben


Buffer component

It gives the buffer capacity to formulation at desire Ph

Sodium citrate, Sodium Phosphate



Increases suspendability and stability of suspension

Polysorbate 80,20


Cation chelating agent Forms

chelate with ions present in the formulation and increases the stability

Disodium EDTA


Suspending Agents

Increases viscosity and suspendability of suspension




Helps to improve solubility

Alcohol, PEG 400, Propylene Glycol



Used to maintain humidification in the formulation


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