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Transcript of nasal drug delivery system
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NASAL DRUG DELIVERY SYSTEM
PRESENTED BYNeha singhM.pharm 1 yr.
GUIDED BYV.B pokharkarHod Pharmaceutics
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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%
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Oral Inject-able Mucosal
Trans-derma
lOcular
Vaginal/Anal
Needle
Needle-less
Nasal
Buccal
Pulmo-nary
Active
Passive
Topical
DRUG DELIVERY STSTEM
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GLOBAL DRUG DELIVERY MARKET BY
ADMINISTRATION MODE
Oral 53%
Inhation 32%
Transdermal 8%
Injectable/Implant 3%
Ocular 2%Nasal 2%
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Nasal Drug Delivery
New Chemical Entity
$50 mio
$300-600 mio
DRUG DEVELOPMENT COST
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New Chemical Entity
Nasal drug Delivery2 – 5 years
10 – 14 years
DRUG DEVELOPMENT TIME
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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
INTRODUCTION
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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.
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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.
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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.
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ANATOMY OF NOSE
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Site of drug
spray &
absorption
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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.
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Olfactory mucosa
Highly vascular nasal mucosa
BrainCSF
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MECHANISM OF DRUG ABSORPTION
Paracellular transport
• Aq route of transport.• Slow and passive.
Transcellular transport
• Transport through lipoidal membrane
• Active transport via carrier mediated means.
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FORMULATION DEVELOPMENT
Dosage form
Formulation considerations
Factors affecting drug absorption
Physiological
Pharmaceutical
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DOSAGE FORMS
Liquid drop
Liquid spray/nebulizers
Suspension spray/nebulizers
Gel
Sustained release
Aerosol
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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
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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
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PHYSIOLOGICAL FACTORS
1. Blood flow
2. Enzymatic degradation
3. Volume of administration
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METHODS TO ENHANCE NASAL ABSORPTION
OF DRUGS
Structural modification
Formulation design
Salt or ester formation
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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.
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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
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Zero order transdermal permeation kinetic=
Plasma concentration=
First order transnasal permeation kinetic=
Plasma concentration=
PHARMACOKINETICS OF NASAL ABSORBTION
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APPLICATIONS
Delivery of non-peptide pharmaceuticals
Delivery of diagnostic drugs
Delivery of peptide-based
pharmaceuticals
Cns delivery through nasal route
Nasal vaccination
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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:
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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:
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Diagnostic agents such as
Phenolsulfonphthalein – kidney function
Secretin – pancreatic disorders
Pentagastrin – secretory function of gastric acid
3. Delivery of diagnostic drugs
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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.
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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
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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.
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SPRAY PUMP DEVICES
- Unidose
- Bidose
- Multidose
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DOSAGE FORMS
Liquid drop
Liquid spray/nebulizers
Suspension spray/nebulizers
Gel
Sustained release
Aerosol
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Nasal drops
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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 .
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Nasal sprays
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Both solution and suspension formulations can be formulated into nasal sprays.
Deliver an exact dose from 25 to 200 μm.
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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.
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Nasal Gels Nasal gels are high-viscosity thickened solutions or suspensions. Advantages of a nasal gelReduction 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.
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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.
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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.
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Nasal vaccines
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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 influenzaIntra nasal H1N1 vaccine Nasovac by Serum Institute
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Therapeutic class of drugs for nasal
route
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1. 2 adrenergic agonists
2. Corticosteroids
3. Antiviral
4. Antibiotics
6. More recently, vaccines
5. Antifungal
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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.
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CASE STUDY
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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.
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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.
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RESULT AND DISCUSSION:
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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.
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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.