Nasopulmonary Drug Delivery System (NPDDS)

Nasopulmonary Drug Delivery System

CONTENTS

—  Introduction

—  Advantages
And Disadvantages

—  Anatomy
& Physiology of Nasal Cavity

—  Mechanism
of Drug Absorption

—  Formulation
Approaches

—  Evaluation
Test

—  Marketed
Preparations

—  Patented
Preparations

—  Recent
Advances

—  Conclusions

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

NASAL DRUG
DELIVERY

INTRODUCTION:

—  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.

ADVANTAGES

—  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.

DISADVANTAGES

•       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.

ANATOMY
& 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
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.

ANATOMY OF
NASAL CAVITY

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.

LIMITATIONS
of NPDDS

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

MECHANISM OF DRUG ABSORPTION

•       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. 

THEORIES OF
MUCOADHESION

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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