Nasal Drug Delivery System

Nasal Drug Delivery System

• Drugs are administered through the nasal route to achieve systemic bioavailability.

Factors Influencing Nasal Drug Absorption

• Systemic bioavailability is affected by several factors

Physiochemical Properties of Drug

• Molecular size is a key property.
• The lipophilic-hydrophilic balance affects absorption.

Nasal Effect

• Membrane permeability influences drug passage.
• Environmental pH impacts absorption.
• Mucociliary clearance affects residence time.

Enzymatic Degradation

• Breakdown of the drug by enzymes affects availability.

Delivery Effect Factors

• Formulation characteristics: concentration, pH, osmolarity, and viscosity.
• Drug distribution and deposition in the nasal cavity matters.
• The delivery device is an important factor

Formulations Factors

• The pH of the formulation and nasal surface affects drug permeation.
• To avoid nasal irritation, the pH of the nasal formulation should be adjusted to 4.5–6.5.

Advantages of Nasal Drug Delivery

• Large nasal mucosal surface area allows dose absorption.
• Rapid drug absorption is achieved through highly-vascularized mucosa.
• Action has a rapid onset.
• Administration is easy and non-invasive.
• First-pass metabolism is avoided
• Improves bioavailability
• Vaccines can be delivered directly to lymphatic tissue.
• Can be a lower dose, reducing side effects.
• Improves patient convenience and compliance.
• Can be self-administered.

Disadvantages of Nasal Drug Delivery

• Smaller absorption surface compared to the gastrointestinal tract (GIT).
• Nasal irritation can occur.
• Limited absorption due to the mucous layer and mucocilliary clearance.

Pathway of Absorption

• Drugs enter through the nose cavity.
• Absorption occurs via the olfactory epithelium directly to the brain.
• Alternatively, absorption may occur through the respiratory epithelium to the systemic circulation.

How to Increase Bioavailability

• Use absorption enhancers.
• Increase residence time.
• Decrease enzymatic degradation.
• Modify drug structure to change physicochemical properties.

Applications of Nasal Drug Delivery

• For local effect, such as oxymetazoline.
• For systemic effect, such as desmopressin.
• For brain targeting, such as zolmitriptan.
• For vaccine delivery, such as the human influenza vaccine (FluMist®).

Nasal Drug Delivery System Dosage Forms

• Liquid dosage forms: solutions, suspensions & emulsions, nasal drops, sprays, and washes.
• Semi-solid dosage forms: nasal gels, creams, and ointments.
• Solid dosage forms: nasal powders.
• Novel drug formulations: carriers like liposomes, microspheres, and nanoparticles.

Liquid Nasal Formulations

• These are typically aqueous solutions, suspensions, or emulsions of the drug.
• Nasal drops are the simplest way to deliver a liquid.
• They have lower microbiological and chemical stability, requiring preservatives.
• Nasal emulsions benefit local applications because of their viscosity.

Delivery Devices for Liquid Dosage Forms

• Instillation and rhinyle catheter: delivers drops to a specified region of the nasal cavity easily and are used mainly during experimental studies.
• Droppers (Squeezed bottle): are mainly used to deliver OTC products like topical decongestants.
• The dose and particle size vary with the force applied.
• When pressure is released, nasal secretions and microorganisms can be sucked into the bottle.
• Nasal Spray (Metered-dose pump system): delivers controlled doses. Developed 50 years ago, can deliver solutions, suspensions, or emulsions.
• Particle size and dose volume are important factors for controlling delivery.

Application Drawbacks

• Direct contact of the spray nozzle tip during actuation can cause mechanical irritation and injury, potentially leading to nosebleeds, crusting, erosions, or perforation.
• High-speed impaction and low temperature may cause unpleasant sensations, reducing patient acceptance and compliance.

Semi-Solid Dosage Forms

• Semi-solid systems like gels, ointments, and liquid systems containing polymers that gel at particular pH changes are used for nasal drug delivery systems.

Nasal Gel

• Gels are semisolid preparations (high-viscosity thickened solutions or suspensions) where the drug is dispersed in a polymeric matrix.
• Gels reduce mucociliary clearance by increasing viscosity, leading to deposition in the anterior portion of the nose.
• Gels mask the unpleasant taste due to reduced accessibility of the formulation to the nasopharynx.
• Advantages include reduced loss of formulation from the nostril during breathing or sneezing, minimized irritation from soothing excipients, and enhanced retention time.
• A limitation is that they are less spreadable due to high viscosity.

Powder Dosage Form for Intranasal Delivery

• Good for unstable drugs.
• Powdered drug residence in the nose can be improved compared to liquid formulations.

Factors to Consider During Preparation of Nasal Powder

• Amount and solubility of the drug.
• Particle size and shape.
• Aerodynamic properties and potential irritation of the drug or excipients.
• Selection of proper device.

Nasal Wash

• Nasal wash is a practice that involves pouring a hydro-saline solution into the nose in one nostril allowing the liquid to flow out from the other.

Applications of Nasal Wash

• Helps expel impurities and keeps the mucosa cleansed and moisturized.
• Favors mucociliary clearance.
• Improves breathing.
• Eliminates noxious substances such as virous,