Intranasal drug delivery system..general presentations

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2. 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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3.  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
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4.  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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5.  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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6.  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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7.  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
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8.  Anatomy and Histology of Nasal Cavity
Fig 1. Anatomy and Histology of Nasal Cavity 8

9.  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
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10.  Factors influencing nasal drug absorption
Fig 2 factors influencing nasal drug absorption
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11.  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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12. • Molecular weight
• Lipophilicity
• Pka
• Solubility
 Physiochemical properties of drug
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13.  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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14. Strategies to increase nasal drug absorption
Fig .3 strategies to increase nasal drug absorption
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15.  Polymers used in nasal drug delivery system
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16.  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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17.  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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18. 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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19.  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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20.  Nasal dosage forms
Nasal drops
 Simple and convenient systems .
 Disadvantage is the lack of dose precision.
Nasal sprays
 Both 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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21. 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

22. 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
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23.  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
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Fig.8.

24. The unit-dose
and
the bi-dose system
Mechanical Basic Pump
24Fig.7

25. Nasal drug products for vaccination available in the market
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Fig 5 nasal products in market

26.  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

27.  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.
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