Nasopulmonary Drug Delivery System (NPDDS)

Nasopulmonary Drug Delivery System



  Advantages And Disadvantages

  Anatomy & Physiology of Nasal Cavity

  Mechanism of Drug Absorption

  Formulation Approaches

  Evaluation Test

  Marketed Preparations

  Patented Preparations

  Recent Advances


Session Objectives

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



  In ancient times the Indian Ayurvedic system of medicines used nasal  route for administration of drug and the process is called as “Nasya”

  Intranasal 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.

  However, recently, the nasal mucosa has seriously emerged as a therapeutically viable route for the systemic drug delivery.

  ´Nasal 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

  ´The nasal cavity is an easily accessible route which is generally  well tolerated

  ´It offers lower doses, more rapid attainment of therapeutic blood  levels, quicker onset of pharmacological activity fewer side effects,  high total blood flow per cm3

  In 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.

  The 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.

  It has also been considered to the administration of vaccines.


  Hepatic first pass metabolism avoided.

  Rapid drug absorption and quick onset of action via vascularized mucosa.

  Bioavailability of larger drug molecules can be improved by means of absorption enhancer.

  BA for smaller drug molecules is good.

  Convenient for long term therapy, compared to parenteral medication.

  Drugs possessing poor stability G.I.T fluids given by nasal route.

  Easy and convenient, self-administration

  Easily administered to unconscious patients.


       Pathologic conditions such as cold or allergies may alter significantly the nasal bioavailability.

       The histological toxicity of absorption enhancers used in nasal drug delivery system is not yet clearly established.

       Relatively inconvenient to patients when compared to oral delivery systems since there is a possibility of nasal irritation.

       Nasal cavity provides smaller absorption surface area when compared to GIT.



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 leucine,CYP450,Transaminase,etc.

The nasal cavity consists three main regions:

1)      Nasal vestibule

2)      Respiratory region

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.

       Normal pH of the nasal secretions in adult à 5.5-6.5.

       Infants and young children à 5.0- 6.7.

       Nasal 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

 b) Olfactory region 

c) Respiratory region

Nasal cavity is covered with mucous membrane which contains goblet cells and secrets mucous

Nose brain pathway

Ø  The olfactory mucosa (smelling area in nose) is in direct contact with the brain and CSF.

Ø  Medications absorbed across the olfactory mucosa directly enter the brain.

Ø  This area is termed the nose brain pathway and offers a rapid, direct route for drug delivery to the brain.


  1. The absorption enhancers used to improve nasal drug  delivery system may have histological toxicity which is  not yet clearly established
  2. Absorption surface area is less when compared to GIT.
  3. Once the drug administered cannot be removed.
  4. Nasal irritation.
  5. There is a risk of local side effects and irreversible damage of the cilia on the nasal mucosa


       Paracellular (intercellular) Slow and passive absorption of peptides and proteins associated with intercellular spaces and tight junctions.

       Transcellular: Transport of lipophilic drugs passive diffusion/active transport.

       Transcytotic: Particle is taken into a vesicle and transferred to the cell. 



Mechanism of bioadhesion


Electronic theory


Attractive electrostatic forces between  glycoprotein mucin network and the bioadhesive  material

Electron transfer occurs between the two forming  a double layer of electric charge at the interface

Adsorption theory


Surface forces resulting in chemical bonding

Strong primary forces: covalent bonds.

Weak secondary forces: ionic bonds, hydrogen  bonds and van der Waal’s forces

Wetting theory


Ability of bioadhesive polymers to spread and  develop intimate contact with the mucus  membranes

Spreading coefficients of polymers must be  positive Contact angle between polymer and cells  must be near to zero

Diffusion theory


Physical entanglement of mucin strands and the  flexible polymer chains Interpenetration of  mucin strands into the porous structure of the  polymer substrate

For maximum diffusion and best bioadhesive  strength: solubility parameters (δ) of the  bioadhesive polymer and the mucus  glycoproteins must be similar

Fracture theory


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 strands,  hence appropriate to study the bioadhesion of  hard polymers, which lack flexible chains


Factors 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.

2. Lipophilicity:-

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 paracellular route.

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.

4. Drug concentration:-

The absorption of drug through nasal route is increased as concentration is increased.

E.g. 1-tyrosine shows increased absorption at high concentration in rate.

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