karan swami intranasal drug-delivery
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1
SEMINAR ON
Formulation and Evaluation of Nasal Drug Delivery System
PRESENTED BY: Mr. Karan B. Swami(M. Pharm. Sem. -II )Dept. of Pharmaceutics
GUIDED BY: Dr. A. J. Shinde Asso.prof. of Pharmaceutics
BHARATI VIDYAPEETH COLLEGE OF PHARMACY, KOLHAPUR.2015-2016
DATE- 11/03/2016
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Introduction
Advantages
Limitation
Anatomy and physiology of nasal cavity
Barriers to nasal absorption
Factors influencing nasal drug absorption
Strategies to increase nasal drug absorption
Evaluation
Conclusion
References
Contents
3
Introduction
Introduction of nasal route as a alternative drug delivery to other
convention drug delivery.
Intranasal drug delivery enables dose reduction/rapid attainment of
therapeutic blood level.
The lipophilic drug are well absorbed from nasal cavity with
pharmacokinetics profile
Drugs ranging from peptides, hormones and vaccines are delivered
through nasal cavity.
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Avoidance of hepatic first-pass metabolism
Avoids degradation of drug in gastrointestinal tract resulting
from acidic or enzymatic degradation
Rate of absorption comparable to IV medication
Results in rapid absorption and onset of effect
Non-invasive, Painless, needle-free administration mode
Easily accessible (even easier to access than IM or IV sites)
Self-medication is possible through this route
Advantages
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Limitations
Adversely affected by pathological condition
Irritation of nasal mucosa by drugs
Enzymatic barrier for permeability of drugs.
Absorption enhancers cause irritation.
Interspecies enhancers cause irritation.
Volume that can be delivered into nasal cavity is restricted
to1-2ml.
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Major functions of the nasal cavity are breathing and olfaction.
Nasal vasculature is richly supplied with blood to fulfill the basic
functions such as heating and humidification, mucociliary clearance
and immunological functions.
Relatively large surface area (~150 cm2) because of the presence of
~400 microvilli per cell.
It is divided by middle (or nasal) septum into two symmetrical
halves, each one opening at the face through nostrils and extending
posterior to the nasopharynx.
Nasal Cavity, Anatomy and Physiology
7
Anatomy and Histology of Nasal Cavity
Fig 1. Anatomy and Histology of Nasal Cavity 8
Nasal mucosal lining
Enzymes present in nasal cavity
Mucociliary clearance (MCC)
• Lipophilic drugs are generally well absorbed with the
pharmacokinetic profiles identical to those obtained after an I.V
injection and bioavailabilities approaching 100%.
• Ex: fentanyl where the Tmax for both i.v and nasal administration
is 7 min or less and the bioavailability was near to 80%.
• Nasal permeability of polar drugs especially large mol.wt polar
drugs such as peptides and proteins is low.
Barrier to Nasal Absorption
9
Factors influencing nasal drug absorption
Fig 2 factors influencing nasal drug absorption 10
Nasal physiological factors
Huang et al showed that phenylephrine, a vasoconstrictor agent,
inhibited the absorption of acetylsalicylic acid in nasal cavity.
Nasal secretions
• Viscosity of nasal secretion
• Diurnal variation
pH of nasal cavity
Mucociliary clearance (MCC)
• The clearance of a drug product from the nasal cavity is influenced by the
site of deposition.
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• Molecular weight
• Lipophilicity
• Pka
• Solubility
Physiochemical properties of drug
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Properties of the formulation
• pH
• Viscosity
• Osmolarity
• Pharmaceutical excipients
• Area of nasal mucus membrane exposed
• Dosage form
• Device related factor
• Particle size of the droplet or powder .
• Site and pattern of deposition
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Strategies to increase nasal drug absorption
Fig .3 strategies to increase nasal drug absorption14
Polymers used in nasal drug delivery system
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Novel drug formulations
Liposomes
They can effectively encapsulate small and large molecules with a
wide range of hydrophilicity and pKa values .
They enhance nasal absorption of peptides such as insulin and
calcitonin by increasing their membrane penetration.
Novel mucoadhesive multivesicular liposomes for transmucosal
insulin delivery has been investigating.
Liposomal drug delivery systems were also reported as useful for
influenza vaccine and non-peptide drugs such as nifedipine.
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Microspheres Microspheres based on mucoadhesive polymers (chitosan, alginate)
present advantages for IN delivery.
Microspheres may also protect the drug from enzymatic metabolism.
Wang et al. have investigated gelatin microspheres as a IN delivery
system for insulin .
Positive results are found for nasal delivery of
• Metoclopramide microspheres of alginate/chitosan
• Carbamazepine chitosan microspheres
• Carvedilol alginate microspheres
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Nanoparticles
Nanoparticles are solid colloid particles with diameter ranging from
1-1000nm.
They consists of macromolecule and used as adjuvant in vaccines
Nanoparticles offer advantage due to small size but only smallest
Nanoparticle penetrate the membrane.
They penetrate by paracelluar route and limited quantity tight junction
In order 3.9-8.4A .
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Evaluation of nasal drug formulation
In vitro nasal permeation studies
A. In vitro diffusion studies
B. In vivo nasal absorption studies
animal models for nasal absorption studies
a. Rat model
b. Rabbit model
c. Ex vivo nasal perfusion model
d. In vivo bioavailability studies
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Nasal dosage forms
Nasal drops Simple and convenient systems .
Disadvantage is the lack of dose precision.
Nasal spraysBoth solution and suspension can be formulated into nasal sprays
The choice of pump and actuator assembly depend on the particle size
and morphology (for suspensions) and viscosity of the formulation.
Solution and suspension sprays are preferred over powder sprays
because powder results in mucosal irritation .
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Nasal gels
Advantages• Nasal gels are high-viscosity thickened solutions or suspensions.
• Reduction of post nasal drop due to high viscosity
• Reduction of taste impact due to reduced swallowing
• Reduction of anterior leakage of formulation.
Nasal powders
• If solution and suspension dosage forms cannot be developed e.g.
due to lack of drug stability
Advantages • Absence of preservative
• Superior stability
• Local application 21
Common devices : Droppers
Squeeze bottles
Spray pumps / atomizers (Accuspray Nasal
Atomizer, MAD (Mucosal Atomization
Device)
Gel applicators
Nasal Nebulizers (Sinus Nebulizer Rhino Clear)
Pressurised Metered Dose Inhalers (pMDIs) Nasal
Disposable Unit/Bi-dose dispensing devices
Powder Dispensing Systems
Nasal delivery devices
Fig:6 MAD 22
Patient-independent Pumps
To minimize dose and spray variations related to the
patient's hand actuation mode.
(Equdel by Valois Pharma)
Preservative Free Systems (PFS) • To accommodate preservative-free drug formulations.
• Preservatives may induce itching in chronic use
• Can generate some formulation instabilities
• Affect the smell and/or taste of the drug product
(Freepod by Valois Pharma)
Novel nasal spray pumps
23
Fig.8.
The unit-dose and
the bi-dose system
Mechanical Basic Pump
24Fig.7
Nasal drug products for vaccination available in the market
25Fig 5 nasal products in market
Conclusion
In a nut shell, the advantages of IN delivery are numerous and
very importantly it is rapid and non-invasive.
An alternative to parenteral and oral route.
In delivery suitable for both topical or systemic delivery and to
treat both acute and chronic diseases.
It also bypasses the BBB and delivers the drug directly into the
CNS. It reduces systemic exposure and thus reduces the side
effects.
In delivery can be utilized for high molecular- weight drugs such
as peptides and proteins, however, bioavailability is dependent
upon the presence of absorption enhancers.
Another application for in dosing is vaccine therapeutics. 26
References Chien YW, Su KSE, Chang .S,Nasal systemic drug deliver, 2nd
edition, USA:Marcel Dekker;1989.1-38,89-97.
Krishnamoorthy R, Mitra AK. Prodrugs for nasal delivery. Adv
Drug Deliv Rev 1998; 29: 135 146.
Talegaonkar S, Mishra PR. Intranasal delivery: An approach to
bypass the blood brain barrier. Indian J Pharmacol 2004; 36(3): 140-
147
Arora P, Sharma S, Garg S. Permeability issues in nasal drug
delivery. Drug Discover Today 2002; 7(18): 967-975
S. Hirai, T. Yashiki, T. Matsuzawa, H. Mima, Absorption of drugs
from the nasal mucosa of rat, Int. J. Pharm. 7 (1981) 317–325.27
THANK YOU
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