nasal drug delivery

Nasal Drug Delivery

Majed AlghamdiFall 2014 – PSB 825 Controlled Drug release

Presentation assignment by Dr. Monica Chuong

1

BOSTON, MA

Nasal Cavity

•Total surface area of about 150 cm2 in humans

•The three main areas of the nasal cavity are: The vestibular region (baffle system filtering the

airborne particles) The olfactory region (capable of metabolizing

drugs ) The respiratory region (major site for absorption

of drugs)

2

Nasal Cavity

3

Nasal Cavity• The epithelial tissue within the nasal cavity is relatively highly

vascularized

• The cellular makeup of the nasal epithelial tissue consists of ciliated columnar cells, non-ciliated columnar cells, goblet cells and basal cells, with the proportions varying in different regions of the nasal cavity

• Ciliated cells facilitate the transport of mucus towards the nasopharynx.

• Basal cells, which are poorly differentiated, act as stem cells to replace other epithelial cells.

• Goblet cells, which contain numerous secretory granules filled with mucin, produce the secretions that form the mucus layer

4

Epithelial tissue of nasal cavity

5

Junctional Complexes of Nasal Cells

• Nasal epithelial cells are interconnected by narrow belt like structures that totally surround the cells (junctional complexes).

1- the zona occludens, 2- the zona adherens, 3- macula adherens,

• The zona occludens is also known as the tight junction. The normal diameter of the tight junctions in the nasal cavity is considered to be of the order of 3.9– 8.4 A ˚

6

Nasal delivery: Local delivery• Intranasal administration of medicines is the natural choice for

the treatment of topical nasal disorders.

• Among the most common examples are antihistamines and corticosteroids nasal decongestants

• In these cases, intranasal route is the primary option for drug delivery because it allows a rapid symptom relief with a more favorable adverse-event profile than oral or parenteral routes

7

Systemic Nasal Drug Delivery

8

Fundamental Factors Affecting Nasal Absorption

Molecular weight: Absorption of drugs decreases as the molecular weight of drug molecules increases. Mc Martin et al reported a sharp decline in drug absorption having molecular weight greater than 1000Dalton

Lipophilicity Drug concentration: Absorption increases as

concentration of drug increases. 1-tyrosine shows increased absorption at high concentration in rate..

Particle size: Particle size 10-50 microns adheres best to the nasal

mucosa.

PATHWAYS

Possible drug absorption pathways

Nasal delivery: Systemic delivery• This route is easier and more comfortable for the patient than

the parenteral route and it avoids enterohepatic recirculation and gut enzymes

• This naturally makes it attractive for the delivery of peptides and recombinant DNA technology

• However, absorption rates fall off sharply when the molecular weight exceeds 1000 Daltons which probably explains why desmopressin is delivered successfully (m. w. 1069 Daltons), while insulin (m. w. 6000 Daltons approx.) is not

11

Nasal delivery: Systemic delivery• The nasal mucosa demonstrates typical absorption mechanisms.

Water soluble drugs enter via passive diffusion through aqueous channels. As the diffusion path through the nasal mucosa is short, intranasally administered drugs demonstrate a rapid rise to peak plasma concentrations, but the rapid clearance from the mucosa limits available time for absorption

• Amino acids such as tyrosine and phenylalanine are absorbed by active transport, presumably by similar mechanisms to those observed in the blood brain barrier

12

Applications of Intranasal Drug Delivery

Nasal Delivery of Organic based Pharmaceuticals

e.g.: Progesterone, Estradiol, Testosterone, Hydralzine, Propranolal, Cocain, Naloxon & Nitrogylcerine. These have shown good Bioavailability by this route.

Water-soluble organic based compounds such as Sodium cromoglycate were also found to be well absorbed.

Nasal Delivery of Peptide-Based Drugs

Nasal delivery: Systemic delivery -Penetration enhancers

• The drive to increase the absorption of large molecular weight molecules has lead to the use of penetration enhancers

• Bile salts, e.g. sodium deoxycholate, sodium glycocholate and sodium taurocholate, decrease the viscosity of mucus and create transient hydrophilic pores in the membrane bilayer

• EDTA, and fatty acid salts such as sodium caprate and sodium laurate, increase paracellular transport by removal of luminal calcium, thus increasing permeability of the tight junctions

14





16

17

34





18

nasal drug delivery

Education