Introduction to Nasal drug delivery system,Anatomy of Nasal cavity,Advantages n limitataions of Nasal DDS,Mechanism,factors affecting Nasal DDS,Formulation,methods to enhance Nasal DDS,Dosage forms,Evalaution

1. PRESENTED BY
B.KAVITHA
M.PHARMACY2NDSEM
PHAMACEUTICS
ROLLNO.13031S0304
JNTUH,CPS,13031S0304

2. INTRODUCTION
Administration of drug through nasal route is referred as Nasal drug delivery system.
Nasal route is an alternative to invasive administrations and provides a direct access to the systemic circulation.
Intranasal Medication administration offers a truly “Needleless ” solution to drug delivery.
In recent years many drugs have been shown to achieve better systemic bioavailability through nasal route than by oral administration
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3. 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
a –nasal vestibuled –middle turbinateb –palatee –superiorturbinate
c –inferior turbinate
f –nasopharynx
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4. 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.
Olfactory
mucosa
Highly vascular
nasal mucosa
Brain
CSF
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5. ADVANTAGES OF NASAL DRUG DELIVERY SYSTEM
1. A non invasiveroute.
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 enhanceror 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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6. 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 lesswhen compared to GIT.
3. Once the drug administered can not be removed.
4. Nasal irritation.
5. There is a risk of local side effects and irreversible damage of the cilia on the nasal mucosa
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7. MECHANISM OF DRUG ABSORPTION
•Aqueousroute of transport.
•Slow and passive.
Paracellular transport
•Transport through lipoidal membrane
•Active transport via carrier mediated means.
Transcellular transport
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8. 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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9. FACTORS AFFECTING DRUG ABSORPTION Drug concentration:
Absorption depends on the initial concentration of the drug The absorption follows first-order kinetics. pH at absorption site:
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.
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10. FACTORS AFFECTING DRUG ABSORPTION
Particle size:
Particle size 10-50 microns adheres best to the nasal mucosa.
Smaller particles pass on to the lungs, larger particles form droplets and run-out of the nose.
Relative lipid solubility
As lipid solubility increases, permeation increases, so lipid soluble drugs are completely absorbed
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11. FACTORS AFFECTING DRUG ABSORPTION
MUCOSAL CONTACT TIME
viscosity increasescontact time which increases the permeation of the drug
MOLECULAR WEIGHT OF THE DRUG
Higher the molecular size, lower the nasal absorption. A good systemic bioavailability can be achieved for molecules with a molecular weight of up to 1000 Daltons when no absorption enhancer is used.
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12. FORMULATION
Drugs
Bioadhesive polymers
Viscosifying agents
Solubilizers
surfactants
Preservatives
Antioxidants
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13. DRUGS
Drugs commonly used are
β2-adrenergic agonist: terbutaline sulphate.
Corticosteroids : budesonide.
Anti cholinergic: ipratropium bromide .
Mast cell stabilizer : sodium chromogylate.
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14. VISCOSIFYING AGENTS
These agents increase the viscosity of the solution prolonging the therapeutic activity of preparation. e.g.: hydroxypropyl cellulose. SOLUBILIZERS
Aqueous solubility of drug always a limitation for nasal drug delivery. e.g.: glycol, alcohol, labrasol, transcutol.
In such cases surfactants or cyclodextrines (HP-β - cyclodextrine) are used , these serve as a biocompatible solubilizer & stabilizer in combination with lipophilic absorption enhancers.
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15. SURFACTANTS
Modify the permeability of nasal mucosa & facilitate the nasal absorption of drugs. E.g. SLS, Poly acrylic acid, sod.glycocholate. BIOADHESIVE POLYMERS
Increases the residence time of drug in nasal cavity and a higher local drug concentration in the mucus lining on the nasal mucosal surface E.g.: Methylcellulose, Carboxymethylcellulose Hydroxyl propyl cellulose
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16. PRESERVATIVES
These are used to prevent the growth of micro organisms. e.g.: parabens, benzalkonium chloride, phenyl ethyl alcohol, EDTA etc. ANTIOXIDANTS
These are used to prevent drug oxidation. E.g.: sodium meta bisulphite , sodium bisulfite, butylated hydroxy toluene& tocopherol etc.
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17. METHODS TO ENHANCE NASAL ABSORPTION OF DRUGS
Structural modification
Formulation design
Salt or ester formation
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18. DOSAGE FORMS
Liquid drop
Liquid spray/nebulizers
Suspension spray/nebulizers
Gel
Sustained release
Aerosol
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19. Nasal drops
Mostsimpleandconvenientsystemsdevelopedfornasaldelivery.
Ithasbeenreportedthatnasaldropsdeposithumanserumalbumininthenostrilsmoreefficientlythannasalsprays.
Disadvantage-lackofthedoseprecision.
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20. Nasal sprays
Bothsolutionandsuspensionformulationscanbeformulatedintonasalsprays.
Deliveranexactdosefrom25to200μm.
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21. Nasal Gels
Nasalgelsarehigh-viscositythickenedsolutionsorsuspensions.
Advantagesofanasalgel
Reductionofpost-nasaldripduetohighviscosity,
Reductionoftasteimpactduetoreducedswallowing,
Reductionofanteriorleakageoftheformulation,
Reductionofirritationbyusingsoothing/emollientexcipientsandtargettomucosaforbetterabsorption.
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22. 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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23. EVALUATION OF NASAL FORMULATION
In vitro nasal permeation studies ( diffusion ):
The nasal diffusion cell is fabricated in glass. The lid has 3 opening, each for sampling, thermometer, and a donor tube chamber. The nasal mucosa of sheep was separated & stoned in distilled water containing few drops at gentamycin injection. mucosal surface is attached to donor chamber tube.
The donor chamber tube is placed such a way that it just touches the diffusion medium in recipient chamber. At predetermined intervals, samples (0.5 ml) from recipient chamber are with draw and transferred to amber colored ampoules. The samples are estimated for drug content by suitable analytical technique .
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24. In Vivo Nasal Absorption studiesRat Model:
The rat is anaesthetized. An incision is made in the neck and the trachea is cannulated with a polyethylene tube. Another tube is inserted through the oesophagus towards the posterior region of the nasal cavity.
The drug solution is delivered to the nasal cavity through the nostril or through the cannulation tubing. The blood samples are collected from the femoral vein. JNTUH,CPS,13031S0304

25. Rabbit Model:
The rabbit is anaesthetized by an intramuscular injection of a combination of ketamine and xylazine. The rabbit's head is held in an upright position and the drug solution is administered by nasal spray into each nostril. During the experiment the body temperature of the rabbit is maintained at 37°C with the help of a heating pad. The blood samples are collected by an catheter in the marginal ear vein or artery.
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26. MARKETED PRODUCTS
Otrivin spray (xylometazoline).
Miacalcin spray (calcitonin).
Vibrocil gel
( phenylephrine,dimethindene maleate).
Naset-p (xylometazoline HCL)-nasal drops.
Nasovac H1N1 vaccine.
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27. 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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28. CONCLUSION
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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29. 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.
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