NASAL DRUG DELIVERY
SYSTEM
PRESENTED BY
Neha singh
M.pharm 1 yr.
GUIDED BY
V.B pokharkar
Hod
Pharmaceutics
1
2
Novel drug delivery is one of the
fastest growing healthcare sectors,
with sales of drugs incorporating
novel drug deliv...
3
Oral
Inject-
able Mucosal
Trans-
dermal
Ocular
Vaginal/
Anal
Needle
Needle-
less
Nasal
Buccal
Pulmo-
nary
Active
Passive...
4
GLOBAL DRUG DELIVERY MARKET BY
ADMINISTRATION MODE
Oral 53%
Inhation 32%
Transdermal 8%
Injectable/Impl
ant 3%
Ocular 2%...
5
Nasal Drug Delivery
New Chemical Entity
$50 mio
$300-600 mio
DRUG DEVELOPMENT COST
6
New Chemical
Entity
Nasal drug Delivery2 – 5 years
10 – 14 years
DRUG DEVELOPMENT TIME
 It is also a type of muco-adhesive drug delivery system.
 Intranasal Medication administration offers a truly
“Needlele...
 NASAL ENZYMES:
• Cytochrome p-450 dependent oxygenase , lactate
dehydrogenase , oxydoreductase , acid
hydrolases, estera...
ADVANTAGES OF NASAL DRUG DELIVERY
SYSTEM
1 A noninvasive route.
2. Hepatic first – pass metabolism is absent.
3. Rapid dru...
LIMITATIONS
1. The absorption enhancers used to improve nasal drug delivery
system may have histological toxicity which is...
ANATOMY OF NOSE
11
12
13
Site of drug
spray &
absorption
NOSE BRAIN PATHWAY
 The olfactory mucosa (smelling area in nose) is in direct
contact with the brain and CSF.
 Medicatio...
MECHANISM OF DRUG ABSORPTION
• Aq route of transport.
• Slow and passive.
Paracellular
transport
• Transport through lipoi...
16
FORMULATION DEVELOPMENT
Dosage form
Formulation considerations
Factors affecting drug absorption
Physiological
Pharmace...
17
DOSAGE FORMS
Liquid drop
Liquid spray/nebulizers
Suspension spray/nebulizers
Gel
Sustained release
Aerosol
18
FACTORS AFFECTING DRUG ABSORPTION
Drug concentration
Mucosal contact time
pH of the absorption site
Size of the drug pa...
PHYSIOCHEMICAL PROPERTIES OF
DRUGS
1. Effect of perfusion rate
2. Effect of perfusate volume
3. Effect of solution pH
4. E...
PHYSIOLOGICAL FACTORS
1. Blood flow
2. Enzymatic degradation
3. Volume of administration
20
21
METHODS TO ENHANCE NASAL ABSORPTION
OF DRUGS
Structural modification
Formulation design
Salt or ester formation
Strategies for improving drug availability
in nasal administration:
1.Improve nasal residence time
• Apply drug anteriorly...
FORMULATION EXCIPIENTS
Buffer capacity-citrate buffer
Osmolarity-sodium acid phosphate
Viscosifying agent-carbapol,cellulo...
24
Zero order transdermal permeation kinetic=
Plasma concentration=
First order transnasal permeation kinetic=
Plasma conc...
25
APPLICATIONS
Delivery of non-peptide pharmaceuticals
Delivery of diagnostic drugs
Delivery of peptide-based pharmaceuti...
26
 Drugs with extensive pre-systemic metabolism, such as
- progesterone
- estradiol
- propranolol
- nitroglycerin
- sodi...
27
Peptides & proteins - low oral bioavailability because of
their physico-chemical instability and susceptibility to hepa...
28
Diagnostic agents such as
Phenolsulfonphthalein – kidney function
Secretin – pancreatic disorders
Pentagastrin – secret...
4.CNS delivery through nasal route :
The delivery of drugs to the CNS from the nasal route may
occur via olfactory neuroep...
5.Systemic delivery:
Fast and extended drug absorption
Ex.- analgesics (morphine),
i. cardiovascular drugs(propranolol)
ii...
6.Nasal vaccines
Nasal mucosa is the first site of contact with inhaled
antigens and therefore, its use for
vaccination, e...
SPRAY PUMP DEVICES
- Unidose
- Bidose
- Multidose
32
33
DOSAGE FORMS
Liquid drop
Liquid spray/nebulizers
Suspension spray/nebulizers
Gel
Sustained release
Aerosol
Nasal drops
34
 Most simple and convenient systems
developed for nasal delivery.
It has been reported that nasal drops
d...
Nasal sprays
35
Both solution and suspension
formulations can be formulated into
nasal sprays.
Deliver an exact dose from...
Lincoln Pharma wins patent for a
novel nasal drug delivery system
Presently in India anti-vomiting treatments are availabl...
37
Nasal Gels
Nasal gels are high-viscosity thickened solutions or
suspensions.
Advantages of a nasal gel
Reduction of p...
Mucosal Atomization Device (MAD)
 Device designed to
allow emergency
personnel to delivery
nasal medications as
an atomiz...
Stem Cell Nasal Spray For Parkinson Disease
Significantly Improves Motor Function
Successful intranasal delivery of stem ...
Nasal vaccines
40
Nasal mucosa is first site of contact with inhaled antigens
and, therefore, its use for vaccination, es...
Therapeutic class of drugs for nasal route
41
1. 2 adrenergic agonists
2. Corticosteroids
3. Antiviral
4. Antibiotics
6. M...
CONCLISION
An accessible alternative route for drug administration.
Provides future potential for several drugs through th...
CASE STUDY
43
MATERIAL AND METHOD:
 Zolmitriptan was a gift sample from Natco Labs,
Hyderabad, India.
 Pluronic F-127 and pluronic F-6...
METHOD:
Preparation of nasal gel formulations
Slow addition of polymer, drug and other additive in cold water with
continu...
46
RESULT AND DISCUSSION:
47
48
49
50
51
CONCLUSION
Study revealed that the temperature sensitive
gelling system can be formulated using optimum
concentration of P...
REFERENCES
.Chien, Y.W., Nasal drug delivery. In: chien, W. (Ed.) Novel Drug Delivery
System, 2nd ed. Marcel Dekker, 1985,...
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nasal drug delivery system

  1. 1. NASAL DRUG DELIVERY SYSTEM PRESENTED BY Neha singh M.pharm 1 yr. GUIDED BY V.B pokharkar Hod Pharmaceutics 1
  2. 2. 2 Novel drug delivery is one of the fastest growing healthcare sectors, with sales of drugs incorporating novel drug delivery systems increasing @ an annual rate of 15%
  3. 3. 3 Oral Inject- able Mucosal Trans- dermal Ocular Vaginal/ Anal Needle Needle- less Nasal Buccal Pulmo- nary Active Passive Topical DRUG DELIVERY STSTEM
  4. 4. 4 GLOBAL DRUG DELIVERY MARKET BY ADMINISTRATION MODE Oral 53% Inhation 32% Transdermal 8% Injectable/Impl ant 3% Ocular 2% Nasal 2%
  5. 5. 5 Nasal Drug Delivery New Chemical Entity $50 mio $300-600 mio DRUG DEVELOPMENT COST
  6. 6. 6 New Chemical Entity Nasal drug Delivery2 – 5 years 10 – 14 years DRUG DEVELOPMENT TIME
  7. 7.  It is also a type of muco-adhesive drug delivery system.  Intranasal Medication administration offers a truly “Needleless” solution to drug delivery.  Therapy through intranasal administration has been an accepted as form of treatment in the Ayurvedic system of Indian medicine 7 INTRODUCTION
  8. 8.  NASAL ENZYMES: • Cytochrome p-450 dependent oxygenase , lactate dehydrogenase , oxydoreductase , acid hydrolases, esterases, lactic dehydrogenases, malic enzymes, lysosomal proteinases, steroid hydroxylases etc.  NASAL PH: • Adult nasal secretion pH: 5.5-6.5 • Infants & children : 5-6.7. • Lysosome in the nasal secretion helps as antibacterial & its activity is diminished in alkaline pH. 8
  9. 9. ADVANTAGES OF NASAL DRUG DELIVERY SYSTEM 1 A noninvasive route. 2. Hepatic first – pass metabolism is absent. 3. Rapid drug absorption. 4. Quick onset of action. 5. The bioavailability of larger drug molecules can be improved by means of absorption enhancer or other approach. 6. Better nasal bioavailability for smaller drug molecules. 7. Drugs which can not be absorbed orally may be delivered to the systemic circulation through nasal drug delivery system. 8. Convenient route when compared with parenteral route for long term therapy. 9
  10. 10. LIMITATIONS 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 can not be removed. 4. Nasal irritation. 10
  11. 11. ANATOMY OF NOSE 11
  12. 12. 12
  13. 13. 13 Site of drug spray & absorption
  14. 14. NOSE BRAIN PATHWAY  The olfactory mucosa (smelling area in nose) is in direct contact with the brain and CSF.  Medications absorbed across the olfactory mucosa directly enter the brain.  This area is termed the nose brain pathway and offers a rapid, direct route for drug delivery to the brain. 14 Olfactory mucosa Highly vascular nasal mucosa Brain CSF
  15. 15. MECHANISM OF DRUG ABSORPTION • Aq route of transport. • Slow and passive. Paracellular transport • Transport through lipoidal membrane • Active transport via carrier mediated means. Transcellular transport 15
  16. 16. 16 FORMULATION DEVELOPMENT Dosage form Formulation considerations Factors affecting drug absorption Physiological Pharmaceutical
  17. 17. 17 DOSAGE FORMS Liquid drop Liquid spray/nebulizers Suspension spray/nebulizers Gel Sustained release Aerosol
  18. 18. 18 FACTORS AFFECTING DRUG ABSORPTION Drug concentration Mucosal contact time pH of the absorption site Size of the drug particle Relative lipid solubility Molecular weight of the drug
  19. 19. PHYSIOCHEMICAL PROPERTIES OF DRUGS 1. Effect of perfusion rate 2. Effect of perfusate volume 3. Effect of solution pH 4. Effect of drug lipophilicity 5. Effect of initial drug concentration. 6. Chemical form 7. Polymorphism 8. Partition coefficient 9. Solubility and dissolution 10. Partical size 19
  20. 20. PHYSIOLOGICAL FACTORS 1. Blood flow 2. Enzymatic degradation 3. Volume of administration 20
  21. 21. 21 METHODS TO ENHANCE NASAL ABSORPTION OF DRUGS Structural modification Formulation design Salt or ester formation
  22. 22. Strategies for improving drug availability in nasal administration: 1.Improve nasal residence time • Apply drug anteriorly • Formulation with polymers • Use of biodegradable microspheres 2.Enhance nasal absorption • Increase the rate at which drug passes through nasal absorption. 22
  23. 23. FORMULATION EXCIPIENTS Buffer capacity-citrate buffer Osmolarity-sodium acid phosphate Viscosifying agent-carbapol,cellulose Solublizer-labrasol,surfactants Preservatives-benzalkonium cl,parabens Antioxidants-tocopherols,sodium metabisulphide Humectants-glycerine,sorbitol 23
  24. 24. 24 Zero order transdermal permeation kinetic= Plasma concentration= First order transnasal permeation kinetic= Plasma concentration= PHARMACOKINETICS OF NASAL ABSORBTION
  25. 25. 25 APPLICATIONS Delivery of non-peptide pharmaceuticals Delivery of diagnostic drugs Delivery of peptide-based pharmaceuticals Cns delivery through nasal route Nasal vaccination
  26. 26. 26  Drugs with extensive pre-systemic metabolism, such as - progesterone - estradiol - propranolol - nitroglycerin - sodium chromoglyate can be rapidly absorbed through the nasal mucosa with a systemic bioavailability of approximately 100% 1.Delivery of non-peptide pharmaceuticals:
  27. 27. 27 Peptides & proteins - low oral bioavailability because of their physico-chemical instability and susceptibility to hepato gastrointestinal first-pass elimination Eg. Insulin, Calcitonin, Pituitary hormones etc. Nasal route is proving to be the best route for such biotechnological products 2.Delivery of peptide-based pharmaceuticals:
  28. 28. 28 Diagnostic agents such as Phenolsulfonphthalein – kidney function Secretin – pancreatic disorders Pentagastrin – secretory function of gastric acid 3. Delivery of diagnostic drugs
  29. 29. 4.CNS delivery through nasal route : The delivery of drugs to the CNS from the nasal route may occur via olfactory neuroepithelium Drug delivery through nasal route into CNS has been reported for i. Alzheimer’s disease ii. brain tumours iii. epilepsy iv. pain and sleep disorders. 29
  30. 30. 5.Systemic delivery: Fast and extended drug absorption Ex.- analgesics (morphine), i. cardiovascular drugs(propranolol) ii. hormones (levonorgestrel, progesterone) iii. antiviral drugs Marketed formulation- zolmitriptan and sumatriptan 30
  31. 31. 6.Nasal vaccines Nasal mucosa is the first site of contact with inhaled antigens and therefore, its use for vaccination, especially against respiratory infections, has been extensively evaluated. Ex. Human efficacy of intranasal vaccines include those against influenza A and B virus, proteosoma‐influenza, adenovirus‐vectored influenza, group B meningococcal native, attenuated respiratory syncytial virus and parainfluenza 3 virus. 31
  32. 32. SPRAY PUMP DEVICES - Unidose - Bidose - Multidose 32
  33. 33. 33 DOSAGE FORMS Liquid drop Liquid spray/nebulizers Suspension spray/nebulizers Gel Sustained release Aerosol
  34. 34. Nasal drops 34  Most simple and convenient systems developed for nasal delivery. It has been reported that nasal drops deposit human serum albumin in the nostrils more efficiently than nasal sprays.  Disadvantage-lack of the dose precision .
  35. 35. Nasal sprays 35 Both solution and suspension formulations can be formulated into nasal sprays. Deliver an exact dose from 25 to 200 μm.
  36. 36. Lincoln Pharma wins patent for a novel nasal drug delivery system Presently in India anti-vomiting treatments are available in the conventional form of tablet and injection which take longer time to bring relief. LPL becomes the first company in India to introduce an anti-vomiting treatment in the form of a Nasal spray pump. 36
  37. 37. 37 Nasal Gels Nasal gels are high-viscosity thickened solutions or suspensions. Advantages of a nasal gel 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 to mucosa for better absorption.
  38. 38. Mucosal Atomization Device (MAD)  Device designed to allow emergency personnel to delivery nasal medications as an atomized spray.  Broad 30-micron spray ensure excellent mucosal coverage. 38
  39. 39. Stem Cell Nasal Spray For Parkinson Disease Significantly Improves Motor Function Successful intranasal delivery of stem cells to the brains of rats with Parkinson disease yielded significant improvement in motor function and reversed the dopamine deficiency characteristic of the disease. This was reported as a Rejuvenation Research in journal published by Mary Ann Liebert. 39
  40. 40. Nasal vaccines 40 Nasal mucosa is first site of contact with inhaled antigens and, therefore, its use for vaccination, especially against respiratory infections  Promising alternative to the classic parenteral route, because it is able to enhance the systemic levels of specific immunoglobulin G and nasal secretary immunoglobulin A. Examples of human efficacy of intranasal vaccines include those against influenza A and B virus, proteosoma influenza Intra nasal H1N1 vaccine Nasovac by Serum Institute
  41. 41. Therapeutic class of drugs for nasal route 41 1. 2 adrenergic agonists 2. Corticosteroids 3. Antiviral 4. Antibiotics 6. More recently, vaccines 5. Antifungal
  42. 42. CONCLISION An accessible alternative route for drug administration. Provides future potential for several drugs through the development of safe and efficacious formulations for simple, painless and long‐term therapy. Drugs can be directly target to the brain in order to attain a good therapeutic effect in CNS with reduced systemic side effects. Much has been investigated and much more are to be investigated for the recent advancement of nasal drug delivery system. 42
  43. 43. CASE STUDY 43
  44. 44. MATERIAL AND METHOD:  Zolmitriptan was a gift sample from Natco Labs, Hyderabad, India.  Pluronic F-127 and pluronic F-68 by BASF Corporation, Mumbai, India.  Sodium alginate, sodium carboxy methyl cellulose and polyvinyl pyrrolidone (K-25) of extra pure grade were supplied by Emcure Research Center, Pune, India.  Benzalkonium chloride was procured from Loba Chemicals, Mumbai, India. All other chemicals were of research grade. 44
  45. 45. METHOD: Preparation of nasal gel formulations Slow addition of polymer, drug and other additive in cold water with continuous agitation. The formed mixtures were stored overnight at 4oC. 45
  46. 46. 46
  47. 47. RESULT AND DISCUSSION: 47
  48. 48. 48
  49. 49. 49
  50. 50. 50
  51. 51. 51
  52. 52. CONCLUSION Study revealed that the temperature sensitive gelling system can be formulated using optimum concentration of PF-127 and PF-68 that can gel at the body temperature. Addition of bioadhesive polymers can prolong the release of zolmitriptan that may be helpful for migraine treatment. 52
  53. 53. REFERENCES .Chien, Y.W., Nasal drug delivery. In: chien, W. (Ed.) Novel Drug Delivery System, 2nd ed. Marcel Dekker, 1985, 189-195. Pisal S.S., Paradkar A.R., Mahadik K.R., Kadam S.S., Pluronic gels for nasal delivery of vitamin B12 Part I: Preformulation study, Int. J. Pharm., 2004, 270, 37-45. Devi S.G., Udupa N., Niosomal sumatriptan succinate for nasal administration, Ind. J.Pharm. Sci., 2000, Nov – Dec., 479 – 481. Alexandridis, P., Holzwarth J.F., Hatton, T.A., Macromolecules, 1994,27,2414. Alexandridis, P. & Hatton T.A., Colloids surface A., 1995, 96. Singhare D.S., Khan S., Yeole P.G., Poloxamers: Promosing block co- polymers in Drug delivery, Ind. J.Pharm. Sci. 2005, sept – oct., 523 – 531. 53
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