Nasal drug delivery Flashcards
what are the four cells in the nasal cavity?
1– ciliated columnar cells covered by cilia and microvilli of uniform length;
2 – basal cells;
3 – goblet cells packed with mucus granules - produce mucin;
4 – non-ciliated columnar cells, covered by microvilli of uniform length - attachment of mucin layer
Most of the nasal cavity is lined with mucosal membranes
how does the nose remove particulates depending on size?
Particles greater than 10 microm are generally filtered out by the vibrisae in nostrils;
Smaller particles (5-10 microm) tend to deposit in the nasal passages and are subsequently cleared by the process of mucociliary clearance
Particles less than 2 microm are not normally filtered out and may enter the lungs.
Viruses – 100 nanometers more likely chances to get into the lungs
what is mucocilary clearlance?
Dust and microorganisms are getting entrapped within the viscoelastic mucus blanket lining the nasal passages;
The mucus is then propelled by the claw-like tips of the cilia, beating in a coordinated manner within the periciliary fluid, towards the nasopharynx where the mucus is swallowed or expectorated.
In the nasal cavity, mucus is moved by the cilia at a rate of approximately 10 cm/min and clearance of the bulk of the mucus from the nose to the nasopharynx occurs over 10-20 minutes.
what is the function of nasal mucus?
It entraps substances entering the nasal cavity and participates in the removal of particulates via mucociliary clearance;
The capacity of mucus to hold water permits the humidification of the inspired air and also aids heat transfer;
Approximately 700ml -2 L of mucus are secreted daily within the nasal cavity.
Mucus presents a diffusion barrier to drug adsorption.
what type of medicinal agent is applied by the nasal route?
Drugs for the alleviation of nasal symptoms (nasal allergy, nasal congestion, nasal infection)
Drugs that inactivated in the GI tract following oral administration and where the route is an alternative to injection (including peptides and proteins).
what gives direct connection between the CNS And the atmosphere?
The nasal mucosa is the only location in the body that provides a direct connection between the central nervous system and the atmosphere.
what are the advantages of nasal route for drug administration?
Relatively large surface area (160 cm2) for drug absorption;
Highly vascularised surface of nasal mucosa ensures rapid absorption and onset of action;
Low metabolic activity
Good accessibility and ease of administration
In some cases, drugs can be absorbed directly into the CNS after nasal administration bypassing the tight blood–brain barrier.
what are disadvantages of nasal route for drug administration?
Mucociliary clearance
Mucus barrier
Metabolic activity
Limited to potent molecules - nasal mucosa can only absorb small amount
Lack of reproducibility (common diseases can alter the conditions of the nose)
Adverse reactions (mucosal membranes can be sensitive to irritation)
what are formulation factors which needs to be considered for nasal route?
Molecular weight of drug molecules
pH of the dosage form
Concentration
Particle size
Tonicity of the dosage form
Viscosity
how does molecular weight effect nasal route delivery?
<1000 Da
>6000Da
Molecules with molecular weight < 1000 Da – relatively good systemic bioavailability, no need in penetration enhancers;
Penetration enhancers can increase this molecular weight limit to about 6000 Da.
Beyond 6000 Da it is unlikely that large molecules could be absorbed without causing damage to the nasal cavity;
Drug absorption after nasal administration is very much higher than after oral delivery.
what are the effects of pH on nasal drug delivery?
Mucus layer is slightly acidic (pH 5.5 – 6.5)
Absorption of drugs is generally increased as they become less ionised;
Cationic drugs in ionised form can be retained through binding to negatively charged mucus glycoproteins, which may also reduce their absorption.
The effect of pH on absorption of peptides is more complex than on conventional drugs.
what is the effects of concentrate on nasal drug delivery?
In the majority of cases the absorption of drugs across the nasal mucosa is via passive diffusion (paracellular or transcellular);
Rate of absorption is affected by the concentration of drug in solution at the absorbing membrane;
If the drug is formulated as a solution, the highest concentration possible should be chosen that is compatible with an accurate and reproducible dosing volume;
Care must be taken, as high local drug concentrations over extended periods of time may also cause severe irritation or adverse tissue reactions.
what does particles/droplets in the size range 5-19 micrometers cause?
In general, particles or droplets in the size range 5-10 micro m tend to deposit in the nasal passages
what is the difference between nasal sprays and nasal drops
Nasal drops disperse a drug solution throughout the length of the nasal cavity from atrium to nasopharynx, offering a relatively large area for immediate absorption;
Nasal sprays tend to deposit at the front of the nasal cavity with little of the dose reaching the turbinates.
About 40 % of the administered dose is cleared rapidly within 20 minutes, then a second, slower phase of clearance follows. In this second slower phase, clearance of the drops is much faster then clearance of the spray, probably because most of the spray deposits on non-ciliated regions.
What would be a better way to administer rapidly absorbed drugs via nasal route?
due to the faster clearance of nasal drops are more suitable for rapidly absorbed drugs
drugs which diffuse across the nasal epithelium relatively slowly will need longer contact time and may thereafter be better administered as a spray.
