Template on Poster for: Calcitonin: new delivery systems through nasal route (challenges-advantages.)

1. 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- 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-
Lipophilicity:
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 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- Osteoporosis
in women who
are 5 years past
menopause.
2- Corticosteroid
induced
Osteoporosis.
3- Paget’s
disease.
4-
Hypercalcemia
states (e.g.
neoplasm).
Uses
Rapid
onset
Painless
delivery
method
Escape first pass
hepatic metabolism
Compliance not an issue
easy and fast to deliver to
patients
Fast transfer as nasal cavity
covered by a thin mucosa and
well vascularized
Related to nose
(rhinitis/epistaxis/redness/stuffy
nose/mucosal alterations)
Flushing of face
Hypersensitivity
reactions
(Anaphylaxis)
Hypocalcemia
Headache
Dizziness
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, 2nd 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