Nasopulmonary Drug Delivery System
& Physiology of Nasal Cavity
of Drug Absorption
By the end of this session, students will be able to:
• Defend need for nasopulmonary DDS
• Express advantages and disadvantages of NPDDS
• Explain antomy and physiology of nasal cavity
• Explain mechanisms of absorption
• Enlist the factors affecting nasal absorption
• Discuss factors influencing nasal absorption
ancient times the Indian Ayurvedic system of medicines used nasal route for administration of drug and the
process is called as “Nasya”
drug delivery is now recognized to be a useful and reliable alternative to oral
and parenteral routes. Undoubtedly, the intranasal administration of medicines
for the symptomatic relief and prevention or treatment of topical nasal
conditions has been widely used for a long period of time.
recently, the nasal mucosa has seriously emerged as a therapeutically viable
route for the systemic drug delivery.
drug delivery has received a significant attention in recent years as a convenient and reliable route, not
only for local but also for the systemic
administration of drugs
nasal cavity is an easily accessible route which is generally well tolerated
offers lower doses, more rapid attainment of therapeutic blood levels, quicker onset of pharmacological
activity fewer side effects, high total
blood flow per cm3
general, among the primary targets for intranasal administration are
pharmacologically active compounds with poor stability in gastrointestinal
fluids, poor intestinal absorption and/or extensive hepatic first-pass
elimination, such as peptides, proteins and polar drugs.
nasal delivery seems to be a favorable way to circumvent the obstacles for
blood-brain barrier (BBB) allowing the direct drug delivery in the biophase of
central nervous system (CNS)-active compounds.
has also been considered to the administration of vaccines.
first pass metabolism avoided.
drug absorption and quick onset of action via vascularized mucosa.
of larger drug molecules can be improved by means of absorption enhancer.
for smaller drug molecules is good.
for long term therapy, compared to parenteral medication.
possessing poor stability G.I.T fluids given by nasal route.
and convenient, self-administration
administered to unconscious patients.
conditions such as cold or allergies may alter significantly the nasal bioavailability.
histological toxicity of absorption enhancers used in nasal drug delivery
system is not yet clearly established.
inconvenient to patients when compared to oral delivery systems since there is
a possibility of nasal irritation.
cavity provides smaller absorption surface area when compared to GIT.
& PHYSIOLOGY OF NASAL CAVITY
lThe lining is ciliated, highly vascular and rich
in mucus gland.
lNasal secretions are secreted by goblet cells,
nasal glands and transudate from plasma.
lIt contains sodium, potassium, calcium,
albumin, enzymes like
The nasal cavity
consists three main regions:
Major drug absorption.
15-20 % of the respiratory cells covered by layer of long cilia
size 2-4 μm.
3) Olfactory region
Small area in the roof of the nasal cavity of about 10 cm2
Drug is exposed to neurons thus facilitate it across the
cerebro- spinal fluid.
pH of the nasal secretions in adult à 5.5-6.5.
and young children à 5.0- 6.7.
cavity is covered with a mucous membrane.Mucus secretion is composed of 95%-
water,2%-mucin,1%-salts,1%-of other proteins
Such as albumin,lysozyme and lactoferrin and 1%-lipids.
It is divided in to two halves by nasal septum.
It contains 3 regions
a) Nasal vestibule
c) Respiratory region
Nasal cavity is covered with mucous membrane which contains
goblet cells and secrets mucous
olfactory mucosa (smelling area in nose) is
in direct contact with the brain and CSF.
absorbed across the olfactory mucosa directly enter the brain.
area is termed the nose brain pathway and offers a rapid, direct route for drug
delivery to the brain.
absorption enhancers used to improve nasal drug delivery system may have histological
toxicity which is not yet
surface area is less when compared to GIT.
the drug administered cannot be removed.
is a risk of local side effects and irreversible damage of the cilia on
the nasal mucosa
MECHANISM OF DRUG ABSORPTION
(intercellular) Slow and passive absorption of peptides and proteins
associated with intercellular spaces and tight junctions.
Transport of lipophilic drugs passive diffusion/active transport.
Particle is taken into a vesicle and transferred to the cell.
Mechanism of bioadhesion
Attractive electrostatic forces between glycoprotein mucin network and the
Electron transfer occurs between the two forming a double layer of electric charge at the
Surface forces resulting in chemical bonding
Strong primary forces: covalent bonds.
Weak secondary forces: ionic bonds, hydrogen bonds and van der Waal’s forces
Ability of bioadhesive polymers to spread and develop intimate contact with the
Spreading coefficients of polymers must be positive Contact angle between polymer and
Physical entanglement of mucin strands and the flexible polymer chains Interpenetration
For maximum diffusion and best bioadhesive strength: solubility parameters (δ) of
Analyses the maximum tensile stress developed during detachment of the BDDS from the mucosal surfaces
Does not require physical entanglement of bioadhesive polymer chains and mucin
affecting nasal absorption
1. Molecular weight:-
The nasal absorption of drugs decreases as the molecular weight increases.
Martin reported a sharp decline in drug absorption having
molecular weight greater than 1000 daltons.
Absorption of drug through nasal route is dependent on the
lipophilicity of drugs.
E.g. Alprenolol and Propranolol which are lipophilic, has
greater absorption than that of hydrophilic Metoprolol.
3. pH of solution:-
pH should be opbarriers timum for maximum absorption.
Nonionised lipophilic form crosses the nasal epithelial via
transcellular route and hydrophilic ionized form passes through the aqueous
E.g. Decanoic acid shows maximum absorption at pH 4.5.
Beyond this it decreases as solution becomes more acidic or basic.
Nasal absorption is pH dependent .Nasal pH in nasal
secretion of adult: 5.5-6.5.In infants and children: 5-6.7. It becomes alkaline in conditions such as
acute rhinitis, acute sinusitis. Lysozyme in the nasal secretion helps
as antibacterial and its activity is diminished in alkaline pH.
The absorption of drug through nasal route is increased as
concentration is increased.
E.g. 1-tyrosine shows increased absorption at high concentration
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