The Pharmaceutics and Compounding Laboratory
Intranasal Preparations

Introduction


Physiology of the Nose

The nose is a facial structure made of cartilage and bones, and covered with skin. Its primaty function is to serve as a channel for transporting air to the lungs as part of the respiratory system. The adult nasal cavity has a capacity of about 20 mL, a very large surface area for absorption, and a very rich blood supply. The air is warmed by the rich blood supply of the nose and humidified while passing through the nose on the way to the lungs. Dust, bacteria, and other matter are entrapped by mucus and swept by cilia through the nasal passageways until the materials can be swallowed, destroying much of the harmful material.

Nasal fluids are normally in the pH range of 5.5 to 6.5. Lacrimal fluids, as well as fluids from the four paranasal sinuses, drain through the nasal cavities, where they are also swallowed. The nose contains olfactory receptors that give the sense of smell which plays an important role in the complexity of tastes.

Intranasal Preparations

The common intranasal liquid dosage forms, solutions and suspensions, can be prepared as drops, squeeze sprays or bottles with MDI valves, nebules, and aerosol intranasal inhalers. Intranasal gels in water miscible base, which are applied to the inside of the nares, can also be prepared. Intranasal solutions should be isotonic, equivalent to 0.9% sodium chloride. The isotonicity will prevent damage to the cilia; damaged cilia cease their natural movements. Osmotic pressures ranging from 200-600 mOsmol/L are acceptable for intranasal administration, although the isotonicity of resident nasal fluids is about 300 mOsmol/L.

Listed below are many of the acceptable characteristics for intranasal solutions. To achieve these characteristics, intranasal preparations contain many of the same excipients fouud in ophthalmic formulations. This commonality is found in vehicles, buffers, preservatives, tonicity adjusting agents, gelling agents, and antioxidants.

    Characteristics of an Acceptable Intranasal Solution
    pH in the range of 5.5-7.5 (4-8 is acceptable)
    Mild buffer capacity
    Isotonic (0.6%-1.8% sodium chloride equivalent is acceptable)
    Does not modify the normal mucus viscosity (e.g., not too hypertonic or hypotonic)
    Does not interfere with normal ciliary motion
    Does not interfere with normal ionic composition of nasal secretions
    Compatible with active ingredients
    Stable
    Sterile
    Preserved