brain targeted drug delivery

1. PRESENTED BY
SHUBHAM RADHESHAM BIYANI
M. PHARMACY (PHARMACEUTICS)
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2. 1. INTRODUCTION
2. ANATOMY & PHYSIOLOGY OF NOSE ALONG WITH NOSE BRAIN PATHWAY
3. BARRIARS OF NASAL ABSORPTION
4. MECHANISM OF NASAL ABSORPTION
5. FACTOR AFFECTING NASAL ABSORPTION
6. ADVANTAGES & LIMITATION
7. APPROCHES FOR ENHANCEMENT IN ABSORPTION
8. PENETRATION ENHANCERS
9. FORMULATION
10. DELIVERY SYSTEM
11. MARKETED PRODUCT EXAMPLES
12. EVALUATION
13. APPLICATION
14. CONCLUSION
15. REFERENCES
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3.  Administration of drug through nasal route is referred as nasal drug
delivery system.
 Nasal route is an alternative to invasive administrations & provides a
direct access to the systemic circulations.
 Intranasal medication administration offers a truly “needleless”
solution to drug delivery.
 About 2% of overall drug delivery is administered via nasal route.
 Topical decongestants or anti-inflammatory drug used to treat rhinitis
or allergy related indications are well known drug product.
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4. Anatomy
it is divided into two halves
by nasal septum , it contains 3
region.
a) Nasal vestibule
b) Olfactory region
c) Respiratory region
Nasal cavity is covered with
mucus membrane which contains
goblet cells and secrets mucus.
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5.  The olfactory mucosa (smelling area of nose) is in direct
contact with the brain and CSF.
 Medication absorbed across the olfactory mucosa directly
enters the brain .
 This area is termed the nose brain pathway and offers a
rapid, direct route for drug delivery to brain .
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6. Nasal blood flow : external & internal carotid arteries .
Nasal secretions : goblet cells, nasal glands , lacrimal glands ..
Composition : 95% water, 1-2 % salts 2-3% mucin in trace amount
Na , K, Ca, Albumin also presents
Nasal enzymes : monooxygenase , lactate dehydrogenase , oxidoreductase
, phosphatase , hydrolases , esterases etc .
Nasal pH : 5.5 -6.5 (adults)
5.0- 6.7(infants & child)
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7. Low Bioavailability
it is due to low membrane permeability (limiting factor for high
mol. Weight polar drug like protein and peptides )
Low membrane transport
 rapid clearance of administered formulations due to MCC
 Ex. Liquid & powder formulation shows rapid clearance.
Enzymatic degradation
Degradation of protein and peptides by exopeptidase and endopeptidase .
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8. •Aqueous route of transport
•Slow & passive
Paracellular
transport
•Transport through lipoidal
membrane
•Active transport via carrier
mediated means
Transcellular
transport
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9. Drug concentration
pH of absorption site
Size of drug particle
Relative lipid solubility
Mucosal contact time
Molecular weight of drug
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10.  Non invasive route
 Avoid hepatic first pass metabolism
 Rapid drug absorption
 Quick onset of action
 Bioavailability of larger molecule can be improved by
absorption enhancer.
 Convenient route.
Limitations
 Absorption enhancer are histologically toxic.
 Absorption surface is less as compared to GIT.
 Once the drug administered cannot removed .
 Nasal irritation etc………….
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11.  Nasal enzyme inhibitors
 Formulation design
 Modifying drug structure / salt or ester formation
e.g. chemical modification of salmon calcitonin ( C-N bond
replaces the S-S bond ) showed better bioavailability than salmon
calcitonin
 Product approach
 Particulate drug delivery
 Absorption enhancers.
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12. Type example
surfactants Sodium dodecyl sulphates ,
Polyoxyethylene – 9 – lauryl ether ,
saponin
Complexing and chelating agents EDTA , salicylates
Cyclodextrins and derivatives α -, β- , γ- cyclodextrin , DMβ-
cyclodextrins , HPβ- cyclodextrin
Bile salts Sodium taurocholate
Sodium glycocholate
Fatty acid salts Oleic acid , caprylate ,
Dry microsphere Degradable starch microsphere
dextran microsphere .
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13.  Drug
 Viscosity modifying agent
 Solubilizers
 Surfactants
 Bioadhesive polymer
 Preservatives
 Antioxidants
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14. Liquid drop
Liquid spray/ nebulizers
Aerosol
Suspension spray / nebulizers
Gel
Sustained release
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16.  In vitro nasal permeation studies (diffusion)
 In vivo nasal absorption studies
I. Rat model
II. Rabbit model
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17. Delivery of non –
peptide
pharmaceutical.
Delivery of
peptide based
pharmaceutical
Delivery of
diagnostic drug
CNS delivery
through nasal
route
Nasal
vaccination
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18.  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 .
 Drug can be directly targeted to the brain to attain good
therapeutics effect .
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19.  Chien Y.W. NDDS 2nd edition marcel Dekker 1985, 189-195
 Intranasal drug delivery system –A glimpse to become
maestro journal of applied pharmaceutical science , shivam
upadhyay 01 (03); 2011; 34-44.
 www.google.com
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