This document discusses nasal drug delivery systems. It begins by outlining the advantages and disadvantages of nasal delivery, as well as the anatomy and physiology of the nasal cavity. Key factors that influence nasal absorption are described, including drug properties, nasal physiology, and formulation characteristics. Various dosage forms for nasal delivery are presented, such as liquids, powders, gels, drops, and sprays. Strategies to improve nasal absorption, like permeation enhancers and particulate systems, are also summarized. In conclusion, nasal delivery provides benefits over injections by being non-invasive and needle-free.

1. Nasal Drug Delivery System
Presented by
Akansha sharma
Mpharma
2 semester
Presented to:
Dr. Tejal Mehta
Head Of Department
Pharmaceutics Deparment
IPNU

2. Content
 Advantage and Disadvantage of nasal drug delivery system
 Anatomy and physiology of Nasal Drug delivery system
 Factor influencing nasal drug delivery system
 Formulation development
 Marketed formulation
 Conclusion

3. The problem !!!
NEEDLE STICKS
 Nasal drug delivery is attractive not because it is better than injection
therapy
 But
 …..It is safer
 …..No needle

4. Advantage of nasal drug delivery system
 Large nasal mucosal surface area for dose absorption
 Rapid drug absorption via highly-vascularized mucosa
 Rapid onset of action
 Ease of administration, non-invasive
 Avoidance of the gastrointestinal tract and first-pass metabolism
 Improved bioavailability
 Lower dose/reduced side effects
 Improved convenience and compliance
 Self-administration.

5. Disadvantage
 Nasal cavity provides smaller absorption surface when compared to GIT.
 Relatively inconvenient to patients when compared to oral delivery since
there is possibility of nasal irritation.
 The histological toxicity of absorption enhancers used in the nasal drug
delivery system is not yet clearly established.

6. Anatomy and Physiology of Nasal Drug Delivery System
 The nasal cavity is divided into two halves by the nasal septum and extends
posterior to the nasopharynx, while the most anterior part of the nasal cavity,
the nasal vestibule, opens to the face through the nostril.
 The nasal cavity consists three main regions are nasal vestibule, olfactory
region and respiratory region.

7.  The nasal cavity is covered with a mucous membrane which can be divided
into two areas; non olfactory and olfactory epithelium.
 The mucus secretion is composed of about 95% water, 2 % mucin, 1% salts, 1%
of other proteins such as albumin, immunoglobulins, lysozyme and lactoferrin,
and 1% lipids.
 The mucus secretion gives immune protection against inhaled bacteria and
viruses.
 The pH of nasal secretion is 5.5-6.5 in adults and 5.0-6.7 in infants.

8. Factor Affecting Nasal Absorption
 Low Bioavailability- The most important factor limiting the nasal
absorption of polar drugs and especially large molecular weight polar
drugs such as peptides and proteins is the low membrane
permeability.
 Low membrane transport-Another importance factor is low
membrane transport is the general rapid clearance of the
administered formulation from the nasal cavity due to the mucociliary
clearance mechanism.
 Enzymatic Degradation-Another contributing factor to the low
transport of especially peptides and proteins across the nasal
membrane is the possibility of an enzymatic degradation of the
molecule either within the lumen of the nasal cavity or during passage
across the epithelial barrier.


9. Factors influencing nasal drug absorption
Physiochemic
al properties
of drug
Lipophilic-
hydrophilic
balance
Enzymatic
degradation
in nasal
cavity.
Molecular
size

10. Factors influencing nasal drug absorption
Nasal
Effect
Membrane
permeability
Environmental
pH
Mucociliary
clearance
Cold,
rhinitis

11. FACTORS INFLUENCING NASAL DRUG ABSORPTION
Viscosity
Formulation
(Concentration, pH,
osmolarity)
Drugs distribution and
deposition
Delivery effects
Delivery Effect

12. Physiochemical properties of drug
Molecular size-
• The nasal absorption of drugs decreases as the molecular weight increases
• The rate of permeation is highly sensitive to molecular size for compounds
with MW ≥ 300 Daltons
Lipophilic-hydrophilic balance-
• By increasing lipophilicity, the permeation of the compound normally
increases through nasal mucosa.
• Lipophilic drugs like naloxone, buprenorphine, testosterone and 17a-ethinyl-
oestradiol are almost completely absorbed when administered intranasal
route.
Enzymatic degradation in nasal cavity –
• In case of peptides and proteins are having low bioavailability across the
nasal cavity, so these drugs may have possibility to undergo enzymatic
degradation of the drug molecule in the lumen of the nasal cavity or during
passage through the epithelial barrier.

13. Nasal effect factors
• The water soluble drugs and particularly large molecular weight drugs like
peptides and proteins are having the low membrane permeability.
Membrane permeability -
• the non ionised lipophilic form crosses the nasal epithelial barrier via
transcellular route, whereas the more lipophilic ionized form passes through the
aqueous paracellular route.
Environmental pH-
• Mucociliary clearance is a one of the functions of the upper respiratory tract is
to prevent noxious substances (allergens, bacteria, viruses, toxins etc.) from
reaching the lungs.
Mucociliary clearance -
• it influence the bioavailability of the drug. It is mainly classified into allergic
rhinitis and common, the symptoms are hyper secretion, itching and sneezing
mainly caused by the viruses, bacteria or irritants
Cold, rhinitis -

14. Delivery effect
 The pH of the formulation and nasal surface, can affect a drug’s permeation.
To avoid nasal irritation, the pH of the nasal formulation should be adjusted
to 4.5–6.5 because lysozyme is found in nasal secretions.
 Concentration gradient plays very important role in the absorption /
permeation process of drug through the nasal membrane due to nasal mucosal
damage.
 The sodium chloride concentration of the formulation affects the nasal
absorption. The maximum absorption was achieved by 0.462 M sodium
chloride concentration

15.  Drugs distribution and deposition -The absorption and bioavailability of the
nasal dosage forms mainly depends on the site of disposition. The anterior
portion of the nose provides a prolonged nasal residential time for disposition
of formulation, it enhances the absorption of the drug.
 Viscosity - A higher viscosity of the formulation increases contact time
between the drug and the nasal mucosa thereby increasing the time for
permeation.

16. STRATEGIES TO IMPROVE NASAL ABSORPTION
To improve the nasal residence time
To enhance nasal absorption
To modify drug structure to change
physicochemical properties.

17. Nasal enzyme inhibitors
 Nasal metabolism of drugs can be eliminated by using the enzyme inhibitors.
 Mainly for the formulation of proteins and peptide molecule development
enzyme inhibitors like peptidases and proteases are used.
 The other enzyme inhibitors commonly used for the enzymatic activity are
tripsin, aprotinin, borovaline, amastatin, bestatin and boroleucin inhibitors.

18. Permeation enhancers
 The permeation enhancers are mainly used for the enhancement of
absorption of the active medicament.
 Mainly they work by Inhibiting enzyme activity ,Reducing mucus viscosity or
elasticity ,Decrease Mucociliary clearance, Open tight junctions and
Solubilize or stabilize the drug.
 Classification of chemical penetration enhancer
 includes
 Surfactants: Polyozyethylene-9-lauryl ether, Saponin
 Bile salts: Trihydroxy salts (glycol- and taurocholate),
 Fusidic acid derivatives (STDHF)
 Chelators: Salicylates, EDTA

19. Prodrug approach
 Prodrug approach is mainly meant for optimizing favorable physicochemical
properties such as solubility, taste, odor, stability, etc. Prodrug is usually
referred as pro moiety.
 The prodrug undergoes enzymatic transformation to release the active
medicament, when it crosses the enzymatic and membrane barrier.
 The absorption of peptides like angiotensin II, bradykinin, caulein, carnosine,
enkephalin, vasopressin and calcitonin are improved by prepared into
enamine derivatives.

20. Particulate drug delivery
 Microspheres, nanoparticles and liposomes are all systems which can be used
as carriers to encapsulate an active drug.
 Microspheres are mainly increase the absorption and bioavailability by
adhering to the nasal mucosa and increase the nasal residence time of drug.
 The microspheres prepared by using polymers like dextran, chitosan,
biodegradable starch microspheres successfully improved the bioavailability
of various drugs.
 Liposomes are amphiphilic in nature are well characterized for favorable
permeation of drugs through the biological membranes, so the water soluble
drugs have been delivered to nasal drugs.

22. DOSAGE FORMS-
LIQUID FORMULATION
POWDER FORMULATION
NASAL GEL
NASAL DROP
NASAL SPRAY

23. LIQUID NASAL FORMULATION-
 Advantages-
 humidifying effect is convenient and useful in crusts and drying of
mucous membranes.
 Drawback-
 Microbiological stability, irritation and allergic rhinitis ,short residence
time.

24. Instillation and Rhinyle Catheter
 Catheters are used to deliver the drops to a specified
region of nasal cavity easily.
 The formulation is placed in the tube. One end is
positioned in the nose, and the solution is delivered
into the nasal cavity by blowing through the other end
by mouth

25. Compressed Air Nebulizer-
 Nebulizer is a device used to administer medication in the form of a mist,
inhaled into the lungs.
 These pharmaceuticals are inhaled instead of ingestion.
 Compressed air is filled into the device.
 It is in order to target their effect to the respiratory tract, which speeds
onset of action of the medicine and reduces side effects, compared to other
alternative intake routes.
 This device is not suitable for the systemic delivery of drug by patient
himself.

26. Metered-dose pump spray-
 Solutions, emulsions or suspensions
 The three main types available for local effect are antihistamines,
corticosteroids, and topical decongestants
 Metered- dose pump sprays include the container, the pump with
the valve and the actuator.
 The dose accuracy of metered-dose pump sprays is dependent on
the surface tension and viscosity of the formulation.
 For solutions with higher viscosity, special pump and valve
combinations are available in the market

27. Dry Powder Inhaler
 Active drug is delivered for local or systemic effect via the
pulmonary route .
 It contain solid drug, suspended or dissolved in a non polar volatile
propellant or in dry powder inhaler that is fluidized when the
patient inhales.
 Asthma, bronchitis, emphysema and COPD, diabetes mellitus.
 Operator puts the mouthpiece of the inhaler into their mouth and
takes a deep inhalation, holding their breath for 5-10 seconds .
 Dose less than a few tens of milligrams in a single breath .

28. NASAL GEL
 Nasal gels are high-viscosity thickened solutions or
suspensions.
 The advantages –
 Reduction of post-nasal drip due to high viscosity,
 Reduction of taste impact due to reduced swallowing,
 Reduction of anterior leakage of the formulation,
Reduction of irritation by using soothing/emollient
excipients and target delivery to mucosa for better
absorption.

29. Application
Delivery of non-peptide
pharmaceuticals
Delivery of peptide-based
pharmaceuticals
Delivery of Drugs to Brain
through Nasal Cavity
Delivery of Vaccines
through Nasal Route
Delivery of diagnostic
drugs

30. Delivery of non-peptide pharmaceuticals
 Nasal membrane containing epithelium is highly vascularized and it contains
large surface area it is readily accessible for drug absorption because
presence of nasal turbinates.
 Drugs with extensive pre-systemic metabolism,
 progesterone,
 estradiol,
 propranolol,
 nitroglycerin,
 sodium chromoglyate
 can be rapidly absorbed through the nasal mucosa with a systemic
bioavailability of approximately 100% .

31. Delivery of Peptide-Base Pharmaceuticals
 Peptides & proteins have generally a low oral bioavailability because of their
physicochemical instability and susceptibility to hepato-gastrointestinal first
pass elimination.
 Examples - insulin, calcitonin, pituitary hormones .
 Use of absorption enhancers like surfactants, glycosides, cyclodextrin and
glycols will increase the bioavailability.
 Nasal route is proving to be the best route for such biotechnological products

32. Delivery of Drugs to Brain through Nasal Cavity:
 It is useful in condition like, Parkinson’s disease, Alzheimer’s disease or pain
because it requires rapid and/or specific targeting of drugs to the brain. It
increase the fraction of drug that reaches the CNS after nasal delivery.
 The olfactory region located at the upper remote parts of the nasal passages
offers the potential for certain compounds to circumvent the blood-brain
barrier and enter into the brain.

33. Delivery of Vaccines through Nasal Route
 Nose with nose- associated lymphoid tissue (NALT) acts as an effective site of
immune system, it is called Waldeyer´s Ring in human beings and nasal
secretions mainly contains immunoglobulins (IgA, IgG, IgM, IgE), protective
proteins such as complement as well as neutrophils and lymphocytes in the
mucosa
Main reasons for exploiting the nasal route for vaccine delivery are -
1) the nasal mucosa is the first site of contacts with inhaled pathogens
2) The nasal passages are rich in lymphoid tissue,
3) Creation of both mucosal and systemic immune responses,
4) Low cost, patient friendly, non-injectable, safe

34. Delivery of diagnostic drugs
 Nasal drug delivery system also play very important role in the delivery of
diagnostic agents for the diagnosis of various diseases and disorders in the
body.
 Phenolsulfonphthalein is a diagnostic agent used to diagnose the kidney
function of the patients. Pancreatic disorders of the diabetic patients were
diagnosed by using the ‘Secretin’. And the secretory function of gastric acid
was determined by Pentagastrin.

35. Marketed preparation
MARKETED FORMULATION ACTIVE INGREDIENT
Otrivine adult nasal drop Xylometazoline hydrochloride
0.1w /v
Dymista nasal spray , suspension Azelastinehydrochloride,
fluticasoneproprionate
Imitrex nasal spray sumatriptan
Stimate nasal spray Desmopressin acetate
Miacalcic nasal spray Calcitonin
Vibrocil gel Phenylephrine, dimethindene maleate
Astelin nasal spray Azelastine hydrochloride

36. CONCLUSION
 Nasal drug delivery system is a promising alternative route of administration
for the several systemically acting drugs with poor bioavailability and it has
advantages in terms of improved patient acceptability and compliance
compared to parenteral administration of drugs.
 Alzheimer’s disease or pain because it requires rapid and/or specific targeting
of drugs to the brain and it is a suitable route to produce immune response
against various diseases like anthrax, influenza etc.

37. REFERENCES
 M.Alagusundaram, B.Chengaia Nasal drug delivery system - an overview
,Journal of Science & Technology 2009 , 454-464
 Kumar And Kiran,Strategies & Prospects Of Nasal Drug Delivery System ;
Ijspr,2012 ;Vol3(3):648-658

38. Thank You 