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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

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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

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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

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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

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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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