Axonal Transport and Distribution of Endogenous Calcitonin Gene ...
Calcitonin poster
1
4 th year, Section 6 (class 201 Department of Pharmaceuti Calcitonin ~ New Delivery Systems Through Nasal Route ~ A little Introduction on Nasal Route Nasal drug administration has been used as an alternative route for the systemic availability of drugs restricted to intravenous administration . This is due to the large surface area, porous endothelial membrane, high total blood flow, the avoidance of first-pass metabolism . 1 - Particle size : Optimum particle size to not swallow the drug or lose it with exhaled breath is 3-7 micron . 2 - Molecula r weight : For good absorpti on without enhancer s up to 1000 Dalton . 3 - pH: Absorpti on is higher at a pH lower than the dissocia tion constant (pKa) of the molecule . 4 - Lipophil icity: More lipophil ic drugs are absorbed better . 5 - Drug Conc.: Absorpti on follows 1 st order kinetics , hence it depends on the initial drug Conc . Effect of Physicochemical Properties on Nasal DD Overview on Challenges for Nasal Route Problem Challenge Solution Enzymatic degradation Inhibit nasal enzymes Enzyme inhibitor, prodrugs Mucociliary clearance Overcome it Deposit formulation in anterior cavity Less permeation Enhance drug permeation, modify the membrane Permeation enhancer, Prodrugs Poor physic- chemical properties of drug Improve it Prodrugs, cosolvents Methods To Improve Absorption Permeation enhancers : Fatty acids, bile salts, phospholipids, surfactants, cyclodextrins. Nasal enzymes inhibitors : Enzymes inhibitor like protease and peptidase are used as for the formulation of peptide and protein molecules. Mucoadhesion : Mucoadhesive polymers make intimate contact with biological membrane and penetrate into the tissue surface. A little Introduction on Calcitonin Calcitonin is a 32-amino acid linear polypeptide hormone that is produced in humans by C- cells of the thyroid. It regulates calcium levels in body and is involved in bone building. When taken by shot or nasal spray, it slows the rate of bone thinning. It also relieves pain ofspinal compression fracture. Calcitonin was extracted from the ultimobranchial glands (thyroid-like glands) of fish, particularly salmon. Salmon calcitonin resembles human calcitonin, but is more active. At present, it is produced either by recombinant DNA technology or by chemical peptide synthesis . 1 - Osteoporosi s in women who are 5 years past menopause . 2 - Corticoster oid induced Osteoporosi s . 3 - Paget’s disease . 4 - Hypercalcem ia states (e.g. neoplasm) . Uses R a p i d o n s e t P a i n l e s s d e l i v e r y m e t h o d E s c a p e f i r s t p a s s h e p a t i c m e t a b o l i s m C o m p l i a n c e n o t a n i s s u e e a s y a n d f a s t t o d e l i v e r t o p a F a s t t r a n s f e r a s n a s a l c a v i t y c o v e r e d b y a t h i n m u c o s a a n d o n o s e ( r h i n i t i s / e p i s t a x i s / r e d n e s s / s t u f f y n o s e / m u c o s a l a l t e r a t F l u s h i n g o f f a c e H y p e r s e n s i t i v i t y r e a c t i o n s ( A n a p h y l a x i s ) H y p o c a l c e m i a H e a d a c h e D i z z i n e s s Advantages and Limitations Stability As mentioned before Calcitonin is a 32-amino acid linear polypeptide. Its relatively small size makes it quite stable for formulation. Other than adjusting the pH and ionic strength it doesn’t require the addition of cosolvents . Storage Conditions of the Nasal Spray : Store unassembled nasal spray bottles (at 2-8 degrees C). Don’t freeze . Store bottles that are in use (at 15-30 degrees C) . BAV of Nasal Spray Compared To Injection The bioavailability of current FDA-approved nasal salmon Calcitonin products is poor, averaging only 3% compared to the bioavailability achieved via the alternate subcutaneous injection route. The advent of highly effective and non- irritating absorption enhancement agents n- Dodecyl-beta-Maltoside, affords a practical opportunity to improve its BAV and broaden its uses specially in analgesia. BAV of Nasal Spray with and without Dodecylmaltoside Compared To Injection It is provided as a solution for nasal administration. (Calcitonin – salmon) 2200 I.U per ml NaCl (adjust isotonicity). Benzalkonium chloride (Preservative mainly- could act as penetration enhancer). Hydrochloric acid (adjust pH). Purified water. Example for Marketed Product: Miacalcin ® Assembling the Nasal Spray 1 . Text book of Novel Drug Delivery System by Chien, 2 nd Edition 2 . Webmd.com 3 . Nasal route and drug delivery systems - Pharm World Sci. - by: Türker S . Onur E, Ozer Y 4 . Mayoclinic.org 5 . Drugs.com 6. Highly Bioavailable Nasal Calcitonin - Potential for Expanded Use in Analgesia - Drug Delivery Technology January 2010 Vol 10 No 1. 7 . Design of salmon calcitonin particles for nasal delivery using spray-drying and novel supercritical fluid-assisted spray-drying processes - Int J Pharm – by: Cho W et al . 8. Modern encroachment and provocation in nasal drug delivery system – by: P.R. Patil, V.K. Salve, R.U. Thorat, P.K. Puranik and S.S. Khadabadi. References
-
Upload
marina-ibrahim -
Category
Science
-
view
61 -
download
0
Transcript of Calcitonin poster
4th year, Section 6 (class 2016)Department of Pharmaceutices
Calcitonin ~ New Delivery Systems Through Nasal Route ~
A little Introduction on Nasal RouteNasal drug administration has been used as an alternative route for the systemic availability of drugs
restricted to intravenous administration .This is due to the large surface area, porous endothelial membrane, high total blood flow, the avoidance of first-pass metabolism.
1 -Particle size :
Optimum particle size
to not swallow the drug or lose
it with exhaled
breath is 3-7 micron.
2 -Molecular
weight :For good
absorption without
enhancers up to 1000
Dalton .
3 -pH: Absorption is higher at a pH lower
than the dissociation
constant (pKa) of the
molecule.
4 -Lipophilicit
y: More lipophilic drugs are absorbed
better.
5 -Drug Conc.:
Absorption follows 1st
order kinetics, hence it
depends on the initial drug Conc.
Effect of Physicochemical Properties on Nasal DD
Overview on Challenges for Nasal RouteProblem Challenge Solution
Enzymatic degradation Inhibit nasal enzymes Enzyme inhibitor, prodrugs
Mucociliary clearance Overcome it Deposit formulation in anterior cavity
Less permeationEnhance drug permeation, modify the membrane
Permeation enhancer, Prodrugs
Poor physic-chemical properties of drug Improve it Prodrugs, cosolvents
Methods To Improve AbsorptionPermeation enhancers: Fatty acids, bile salts, phospholipids, surfactants, cyclodextrins.Nasal enzymes inhibitors: Enzymes inhibitor like protease and peptidase are used as for the formulation of peptide and protein molecules.Mucoadhesion: Mucoadhesive polymers make intimate contact with biological membrane and penetrate into the tissue surface.
A little Introduction on CalcitoninCalcitonin is a 32-amino acid linear polypeptide hormone that is produced in humans by C-cells of the thyroid. It regulates calcium levels in body and is involved in bone building. When taken by shot or nasal spray, it slows the rate
of bone thinning. It also relieves pain ofspinal compression fracture. Calcitonin was extracted from the ultimobranchial glands (thyroid-like glands) of fish, particularly salmon. Salmon calcitonin resembles human calcitonin, but is more active. At present, it is produced either by recombinant DNA technology or by chemical peptide synthesis.
1 -Osteoporosis in women who
are 5 years past menopause .
2 -Corticosteroid induced
Osteoporosis.
3 -Paget’s disease.
4 -Hypercalcemia
states (e.g. neoplasm).
Uses
Rapi
d onset
Pai
nl
ess
delivery
method
Escape
first
pass
hepatic
metabolis
m
Co
mpli
ance
not
an
issue
easy
and
fast
to
deliver
to
pati
ents
Fast
transfer
as
nasal
cavity
covered
by
a
thi
n
mucosa
and
well
vascul
arized
Rel
ated
to
nose
(rhi
ni
tis/epistaxis/redness/stuffy
nose/
mucosal
alterati
ons)
Fl
ushi
ng
of
face
Hypersensi
tivity
reacti
ons
(Anaphyl
axis)
Hypocalce
mi
a
Headache
Dizzi
ness
Advantages and Limitations
StabilityAs mentioned before Calcitonin is a 32-amino acid linear polypeptide. Its relatively small size makes it quite stable for formulation. Other than adjusting the pH and ionic strength it doesn’t require the addition of cosolvents.Storage Conditions of the Nasal Spray :Store unassembled nasal spray bottles (at 2-8 degrees C). Don’t freeze .
Store bottles that are in use (at 15-30 degrees C).
BAV of Nasal Spray Compared To InjectionThe bioavailability of current FDA-approved nasal salmon Calcitonin products is poor, averaging only 3% compared to the bioavailability achieved via the alternate subcutaneous injection route.The advent of highly effective and non-irritating absorption enhancement agents n-Dodecyl-beta-Maltoside, affords a practical opportunity to improve its BAV and broaden its uses specially in analgesia.
BAV of Nasal Spray with and without
Dodecylmaltoside Compared To Injection
It is provided as a solution for nasal administration. (Calcitonin – salmon) 2200 I.U per mlNaCl (adjust isotonicity).Benzalkonium chloride (Preservative mainly-could act as penetration enhancer).Hydrochloric acid (adjust pH).Purified water.
Example for Marketed Product: Miacalcin®
Assembling the Nasal Spray
1 .Text book of Novel Drug Delivery System by Chien, 2nd Edition2 .Webmd.com
3 .Nasal route and drug delivery systems - Pharm World Sci. - by: Türker S. Onur E, Ozer Y 4 .Mayoclinic.org
5 .Drugs.com6. Highly Bioavailable Nasal Calcitonin - Potential for Expanded Use in Analgesia - Drug Delivery Technology January 2010 Vol 10 No 1.
7 .Design of salmon calcitonin particles for nasal delivery using spray-drying and novel supercritical fluid-assisted spray-drying processes - Int J Pharm – by: Cho W et al.
8. Modern encroachment and provocation in nasal drug delivery system – by: P.R. Patil, V.K. Salve, R.U. Thorat, P.K. Puranik and S.S. Khadabadi.
References
