INTRODUCTION DELIVERY SYSTEM AND EVALUATION

1. INTRA NASAL
DRUG DELIVERY
SYSTEMS
Sujitha Mary
2nd Semster
M.Pharm
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2. CONTENTS
Introduction
Delivery systems
- nasal liquid formulations
- powder dosage forms
- nasal gels
- others
Evaluation of nasal formulation
Current available formulations
Conclusion
References
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3. INTRODUCTION
Nasal preparations are products applied in the nose to treat
conditions of nose or nasal symptoms.
They include medicines such as steroids, lubricants,
antihistamines , decongestants and anti-infectives used to treat
hay fever symptoms, congestion and infections.
Nasal preparations are available as sprays, drops, creams,
ointments and solutions for irrigation
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4. DELIVERY SYSTEMS
Liquid nasal formulations
Powder nasal formulations
Nasal gels
Others
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5. A. Liquid Nasal Formulations
They are mainly based on aqueous state formulations.
Their humidifying effect is convenient and useful.
Microbiological stability, irritation and allergic rhinitis are
the major drawbacks
Solution and sprays
The drug solution are administered as nasal drops, sprays,
and a metered dose nebulizer.
Suspensions
Prepared by suspending the micronized drug in a liquid
diluent or carrier suitable for application to the nasal mucosa.
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1. Nasal Drops
Nasal drops are one of the most simple and convenient
systems developed for nasal delivery.
The main disadvantage of this system is the lack of the
dose precision and therefore nasal drops may not be
suitable for prescription products.
 It has been reported that nasal drops deposit human
serum albumin in the nostrils more efficiently than nasal
sprays

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PREPARATION OF
NASAL DROPSNasal drops are generally formulated to resemble the nasal secretion.
Simple solution method is employed for the preparation
Formula
Ephedrine hydrochloride 0.1g
Sodium chloride 0.1g
Chlorobutanol(preservative) 0.1g
Water q.s 20ml
Accurately weigh the Chlorobutanol and powder it.
In conical flask take ¾th quantity of water and heat to 60ᵒC with out putting the stopper.
Add Chlorobutanol to hot water and quickly insert the stopper, shake well, solution completes.
Allow the solution to cool and ephedrine hydrochloride and sodium chloride. Dissolve them
by stirring and filter and adjust final volume with water.

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Squeezed Bottle
Squeezed nasal bottles are mainly used as
delivery devices for decongestants.
 They include a plastic bottle with a simple jet
outlet.
 While pressing the plastic bottle the air inside
the container is pressed out of the small
nozzle, thereby atomizing a certain volume.
 By releasing the pressure again air is drawn
inside the bottle.
This procedure often results in contamination
of the liquid by microorganisms and nasal
secretion sucked inside.

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Most of the pharmaceutical nasal preparations in the
market containing solutions, emulsions or suspensions
are delivered by metered-dose pump sprays.
Metered-Dose Pump Sprays

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Nasal sprays, or nasal mists, are used for the nasal delivery
of a drug or drugs, either locally to generally alleviate cold or
allergy symptoms such as nasal congestion or systemically.
Although delivery methods vary, most nasal sprays function
by instilling a fine mist into the nostril by the action of a
hand-operated pump mechanism.
It includes the container ,the pump with the valve and the
actuator.

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MUCOSAL ATOMIZATION
DEVICE(MAD)
Device designed to deliver medication in emergency as
atomized spray.
Reliable atomization of topical solution across the nasal and
oropharyngeal mucous membrane.

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B. POWDER DOSAGE FORMS
Advantages
 Lack of preservatives and administration of large doses of
drugs,
Improved stability of formulation,
Donot support microbial growth,
Compared to solutions,the administration of powders could
result in a prolonged contact with the nasal mucosa.
Powder form is suitable for number of non-peptide drugs
and is well suited for peptide drugs.

14. PREPARATION OF
POWDERS
Reduction of particle size of all ingredients to the same size
range to prevent stratification.
Sieving
Weighing of each ingredient.
Mixing
Packaging
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 Insufflators are the devices to deliver
the drug substance for inhalation.
 It can be constructed by using a straw
or tube which contains the drug
substance and sometimes it contains
syringe also.
 Many insufflator systems work with
pre-dosed powder doses in capsules
 The achieved particle size of these
systems is often increased compared
to the particle size of the powder
particles due to insufficient
disaggregation of the particles.
1) Insufflators

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2) Dry Powder Inhaler
 Dry powder inhalers (DPIs) are devices
through which a dry powder
formulation of an active drug is
delivered for local or systemic effect via
the pulmonary route or intranasal route.
 These are commonly used to treat
respiratory diseases such as asthma,
bronchitis, emphysema and COPD&
diabetes mellitus.A

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Dry powder inhalers are bolus drug delivery devices that contain solid
drug, suspended or dissolved in a non polar volatile propellant or in dry
powder inhaler that is fluidized when the patient inhales.
 The medication is commonly held either in a capsule for manual loading
or a proprietary form from inside the inhaler.

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Dry Powder Inhaler Devices Capsule-based
Storage position ready for inhalationOpen tray and insert capsule
Powder emptying can be confirmed through capsule window which
remains open during inhalation

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Characteristics
Dose range From micro gram to 50
mg
Life time 30-60 capsules(one
month’s use)
components plastic
uses Chronic or acute uses

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Dry Powder Inhaler Devices
Twin Caps
 It was developed specifically for high dose, acute and chronic treatments .
 It is a very simple inhaler, suitable for emergency treatments or in
situations where minimal usage instructions or medical supervision are
available .
 It is low cost and is disposable.
Main features
Contains two factory-filled doses in pre-formed cavities
Extremely easy to use
Foil-pouched for moisture protection

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Uptake inhaler Inhale first dose Push the dose shuttle
Push the button in one direction

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Characteristics
Dose type Two capsule shaped
cavities
Dose range From micro gram to 50
mg
Life time Single use, disposable
Components Plastic
use Acute and short
chronic treatment

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3. Nasal powder sprayers
Fit-lizer.
capsule-based, single-dose powder devices.
When inserted into a chamber, the top and bottom of the
capsule is cut off by sharp blades.
 A plastic chamber is compressed by hand, compressed air
passes through a one-way valve and the capsule during
actuation, the powder is emitted.

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Unidose-DP
 is similar to the Fit-lizer device.
 An air-filled compartment is compressed until a pin ruptures a
membrane to release the pressure to emit the powder.

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4.Pressurized MDIs
A metered-dose inhaler (MDI) is a device that delivers a specific
amount of medication to the lungs, in the form of a short burst of
aerosolized medicine that is inhaled by the patient.
 It is the most commonly used delivery system for treating
asthma, chronic obstructive pulmonary disease (COPD) and other
respiratory diseases.
The medication in a metered dose inhaler is most commonly a
bronchodilator, corticosteroid or a combination of both for the
treatment of asthma and COPD.
 Other medications less commonly used but also administered by
MDI are mast cell stabilizers, such as (cromoglicate or
nedocromil).

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The advantages of MDIs are their portability and small size,
dose consistency, dose accuracy, protection of the contents and
that they are quickly ready for use
To use the inhaler the patient presses down on the top of the
canister, with their thumb supporting the lower portion of the
actuator.
Actuation of the device bring out a metered dose of the
formulation which contains the medication either dissolved or
suspended in the propellant.
 Breakdown of the volatile propellant into droplets, followed by
rapid evaporation of volatile propellant, outcome is the
generation of an aerosol consisting of micrometer-sized
medication particles that are inhaled.

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C.Nasal Gels
Nasal gels are high-viscosity thickened solutions or suspensions.
Advantages
Reduction of taste impact due to reduced swallowing,
Reduction of anterior leakage of the formulation,
Reduction of irritation by using soothing/emollient excipients
and target delivery to mucosa for better absorption.

28. METHOD OF
FORMULATION
1.Fusion method
In this method various waxy materials are employed as gellant in
non polar media.
Drug was added when waxy materials melted by fusion.
2. Cold method
Water was cooled to 4-10ᵒC and placed it in mixing container.
Gelling agent was slowly added and agitating until solution is
complete.
Maintain temperature below10ᵒC .
Drug was added in solution form slowly with gentle mixing.
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29. OTHERS
INSTILLATION AND RHINYLE
CATHETER
Catheters are used to deliver the drops to a specified
region of nasal cavity easily.
The formulation is placed in the tube. One end is
positioned in the nose, and the solution is delivered into
the nasal cavity by blowing through the other end by
mouth
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Compressed Air Nebulizers
Nebulizer is a device used to administer medication in the form
of a gases state, inhaled into the lungs.
These pharmaceuticals are inhaled instead of ingestion.
It is in order to target their effect to the respiratory tract, which
speeds onset of action of the medicine and reduces side effects,
compared to other alternative intake routes.

31. BIO MEDICAL APPLICATIONS OF NASAL DRUG
DELIVERY SYSTEM
Nasal delivery of Organic based pharmaceuticals
Drugs with extensive presystemic metabolism, such as
progesterone, estradiol, Testosterone,Hydralazine, Propronolol,
cocaine, Nalaxone, and nitroglycerine can be rapidly absorbed
through the nasal mucosa with a systemic bioavailability of
approximately 100 %.
Nasal delivery of peptide based pharmaceuticals
Peptide and protein pharmaceuticals have a generally low oral
bioavailability.
Nasal route is providing to be best route for administration of
such drugs.
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Delivery of Drugs to Brain Through Nasal Cavity
This delivery system is beneficial in conditions like Parkinson’s
disease, Alzheimer’s disease or pain because it requires rapid and/or
specific targeting of drugs to the brain.
It increase the fraction of drug that reaches the CNS after nasal
delivery.
The olfactory region located at the upper remote parts of the nasal
passages offers the potential for certain compounds to circumvent the
blood-brain barrier and enter into the brain.
Insulin like growth factor -treatment of diabetis mellitus

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Delivery of Vaccines Through Nasal Route
Delivering the vaccine to the nasal cavity itself stimulates the
production of local secretory IgA antibodies as well as IgG,
providing an additional first line of defense, which helps to
eliminate the pathogen before it becomes established.
Anthrax are treated by using the nasal vaccines prepared by
using the recombinant bacillus anthrasis protective antigen
Delivery of Diagnostic Drugs
Used in delivery of diagnostic agents for the diagnosis of
various diseases and disorders in the body.
 phenolsulfonphthalein –diagnose kidney function
Secretin for pancreatic disorders of the diabetic patients

34. EVALUATION OF NASAL
FORMULATIONS
(a) In vitro nasal permeation studies, various approaches used
to determine the drug diffusion through nasal mucosa
from the formulation.
In Vitro Diffusion Studies
The nasal diffusion cell is fabricated in glass.
The water-jacketed recipient chamber (60 ml),the lid has 3
opening, each for sampling, thermometer, and a donor tube
chamber.
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Procedure
1. The nasal mucosa of sheep was separated from sub layer bony
tissues.
2. stoned in distilled water containing few drops of gentamycin
injection.
3. After the complete removal of blood from muscosal surface, is
attached to donor chamber tube.
4.The donor chamber tube is placed such a way that it just touches
the diffusion medium in recipient chamber.
5. At predetermined intervals, samples (0.5 ml) from recipient
chamber are withdraw and transferred to amber colored ampoules.
6. The samples withdrawn is suitably replaced. The samples are
estimated for drug content by suitable analytical technique.
Temperature is maintained at 37 oC.

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(b) In Vivo Nasal Absorption Studies
Animal Models for Nasal Absorption Studies
The animal models for nasal absorption studies can be of two
types,
Whole animal or in vivo model and an isolated organ perfusion
or ex vivo model.
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Invivo model
1) Rat Model
Procedure
1. The rat is anaesthetized by intraperitoneal injection of sodium
pentobarbital.
2. An incision is made in the neck and the trachea is cannulated
with a polyethylene tube.Another tube is inserted through the
oesophagus towards the posterior region of the nasal cavity.
3.The drug solution is delivered to the nasal cavity through the
nostril or through the cannulation tubing.
4. The blood samples are collected from the femoral vein.

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2) Rabbit Model
1.The rabbit is anaesthetized by an IM injection of a
combination of ketamine and xylazine.
2.The rabbit's head is held in an upright position and the drug
solution is administered by nasal spray into each nostril.
3.During the experiment the body temperature is maintained at
37°C with the help of a heating pad.
4.The blood samples are collected by an indwelling catheter in
the marginal ear vein or artery.

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3)Dog model
The dog is anaesthetised by IV injection of sodium thiopental
and maintained in an anaesthetized state with sodium
phenobarbital.
A positive pressure pump provides ventillation through a cuffed
endotracheal tube,and a heating pad keeps the body temp at 37-
380c.
Blood samples are collected from the jugular vein
4)Sheep model
Same as dog model

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5)Monkey model
The monkey is tranquilized by IM injection of ketamine Hcl
solution or is anaesthetised by IV injection of sodium
phenobarbital.
While holding the head in an upright position,the drug solution
is delivered into each nostril.
The monkey is then placed in a supine position in a metabolism
chair for 5-10 min following intranasal administration.
Blood samples are collected via an indwelling catheter in the
vein

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Ex vivo nasal perfusion model
Same surgical prepartion as that of rat model
During the perfusion studies a funnel is provided underneath the nose to lead
the drug solution,which is flowing out of the nasal cavity,into the drug
reservoir.
The reservoir solution of drug candidate to be evaluated is placed in the
container,which is maintained at 370c,and is circulated through the nasal cavity
of the rat by means of a peristaltic pump.
The perfusion solution passes out from the nostril and through the funnel and
flows into the drug reservoir solution again.
The reservoir is stirred constantly,and the amount of drug absorbed is then
determined by measuring the drug concentration remaining in the solution
after a period of perfusion.

42. CURRENTLY MARKETED
FORMULATION
Sl no product Active ingredient
1 Otrivin adult nasal
drops,sprays
Xylometazoline hydrochloride
0.1%
2 Dymista nasal
spray,suspension
Azelastine
hydrochloride,fluticasone
propionate
3 Imitrex nasal spray Sumatriptan
4 Stimate nasal spray Desmopressin acetate
5 Vibrocil gel Phenylephrine,dimethindene
maleate
6 Astelin nasal spray Azelastine hydrochloride
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43. REFERENCES
Chein YW. Novel drug delivery system.2nd ed.USA:Informa
healthcare;2009.p.229-265
Hiremath SR.Textbook of Industrial pharmacy. Drug delivery system and
cosmetic&Herbal drug technology.Orient longman limited;2008.p.61-71
Chavan p et al. Nasal drug delivery system.Review article. published by
World Journal of Pharmacy and pharmaceutical sciences.2014;3(12)598-617
Moharil S et al. Nasal dosage forms and devices for Intranasal drug
delivery.Review article.Published by World journal of pharmacy and
pharmaceutical sciences.2014;3(4)554-571
Rahisuddin et al. Review on Nasal drug delivery system with recent
advancement. Review article. International Journal of pharmacy and
pharmaceutical sciences.2011;3(2)6-11
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