The document discusses nasal drug delivery systems. Nasal delivery has advantages like easy access, rapid onset of action, and avoidance of first-pass metabolism. Both local and systemic drugs can be delivered nasally. Barriers include mucociliary clearance and enzymatic activity in the nasal cavity. Excipients like co-solvents and suspending agents are used. Liquid drugs are administered via droppers or spray pumps, while performance is tested through parameters like dosage volume and droplet size. Nasal delivery provides local treatment or systemic effects depending on the drug's properties like lipophilicity. Strategies to improve absorption include increasing solubility and permeability.

1. DOSAGE FORM SCIENCE
PRESENTATION ON NASAL DRUG DELIVERY SYSTEM
• GROUP (A)
• GROUP MEMBERS NAME:
ALVINA AHMED (R-011), FILZA SAEED (R-026), MAHA AQIL (R-039), WAHAJ AHMED (R-095), MUHAMMAD
HAMZA (R-053).
Presented to: Dr.Tehmina Maqbool

2. NASAL DRUG DELIVERY
INTRODUCTION
The nasal route of delivery has the advantages of easy access (for local delivery) an rapid
onset of action (due to the rich vascularization of the nasal cavity) and is considered
noninvasive (compared to the parenteral route). Both local and systemic acting drugs can be
delivered via the nasal route. Examples of nasally administered drugs include corticosteroids,
antihistamines, decongestants, calcitonin, triptans and vaccines. Nasal formulations are most
often liquid-based (solution or suspension) dosage forms, which may be administered via
drops or sprays to the nasal cavity. Recently, nasal powder formulations have also been
developed. The use of the nasal route for delivery of drugs to the brain is an area of intense
research focus, as the nasal cavity is innervated and may potentially allow for bypass of the
blood–brain barrier for drug delivery. The most common reason or introducing a drug into the
nasal cavity is to provide a convenient and accessible route or rapidly and efficiently
managing the localized symptoms associated with allergic rhinitis, nasal congestion and nasal
infection.

3. There are several possible reasons or pharmaceutical companies to consider employing
this route or marketed medicines rather than the much more popular (and pre erred)
oral route. These include:
• The potential to elicit a rapid onset of action (e.g. in the
treatment o pain, migraine and erectile dysfunction).
• The avoidance of gastrointestinal and hepatic pre-systemic
metabolism (e.g. for susceptible peptides, such as calcitonin
and other drugs such as hyoscine and morphine), despite the
nasal cavity containing inherent enzymatic activity.
• The lower costs incurred by the pharmaceutical industry (in
comparison to parenteral products) since there is no
requirement of sterilization of the final product.
• The management of chronic disorders; providing the
medicine does not induce irritation then it can be used or
prolonged periods (perhaps alternating the use of nostrils).

4. Barriers for Nasal Drug Delivery
• The nasal cavity contains a mucociliary clearance system that functions to filter large
particles. Ciliated epithelial cells move the mucus layer covering the nasal epithelium
forward toward the nasopharynx.
• This can potentially lead to rapid clearance of deposited drug and may reduce drug
absorption. To improve retention of deposited drug on the nasal epithelium, the use
of gelling agents and bio adhesive polymers (i.e., a natural polymer with adhesive
properties)
• Droplet or particle size distribution of the nasal spray or powder upon actuation from
the device can affect the area of the nasal cavity in which the drug is deposited and
subsequently the therapeutic effect of the delivered drug.
• In general, particles/droplets that are greater than 10 μm in diameter are retained in
the nasal cavities and do not enter the lungs upon inspiration.

5. Excipients Used in Nasal formation

6. • If the drug has low aqueous solubility, the inclusion of co-solvents may be necessary in
order to keep the drug dissolved.
• Suspending agents, such as carboxymethylcellulose sodium and microcrystalline cellulose,
or surfactants, such as polysorbate and polyethylene glycol, may be required if the
formulation is a suspension.
Methods of Nasal Administration
 Liquid nasal formulations may be delivered via droppers, squeeze bottles, pressurized
delivery systems, or mechanical spray pumps systems.
 Many over-the-counter nasal formulations are administered through droppers or squeeze
bottles.
 This dosage form may be better suited for infants, who have a smaller nasal mucosa that is
more easily covered by the drops.
 Squeeze bottles that deliver a spray formulation can reach a larger surface area of the nasal
mucosa than drops but are not a closed system, and microbes can enter the container from
the tip of the bottle and through backflow after administration.

7. Alternative Method
• Alternative to droppers and squeeze bottles are :
1. Metered dose: is defined as the release of a specific amount of
drug by the device upon eachdevice actuation.
2. Nasal spray pumps: are responsible for metering, atomization,
containing and delivery of the formulation to the patient.

8. Nasal Device Performance
Testing
• Performance of nasal delivery systems are affected by the dosage volume, the
spray angle, spray/plume geometry, the size distribution of droplets in the spray,
and in the case of a suspension formulation, the particle size distribution of
suspended particles within the formulation.
• These device and formulation performance parameters vary depending upon the
drug product and are influenced by the viscosity and surface tension of the liquid
formulation as well as the dimensions and mechanics of the device.
• It is particularly important that these parameters remain consistent and
reproducible throughout the lifetime of the drug product, as they affect the
delivery of the drug to the therapeutic target.

9. Local delivery
• For conditions affecting the nose, it is logical to deliver the drug directly to its
site of action. This permits the rapid relief of symptoms with a much lower
dose of drug than would be necessary if it were delivered by the oral route,
and reduces the chance of systemic side effects.
Systemic delivery
• The rationale for the use of the nasal cavity or systemic delivery includes its
accessibility, avoidance of pre-systemic metabolism and potential to provide a
rapid onset of action. Its use for peptides has been successful since, although
only a very low percentage of administered drug is absorbed (i.e. low
bioavailability), the attained plasma levels are sufficient for therapeutic effcacy.

10. Lipophilicity/Hydrophilicity And
Molecular Size
• Lipophilic drugs such as pro-pranolol, progesterone and fentanyl are
rapidly absorbed from the nasal cavity by the transcellular route and
have a nasal bioavailability similar to that obtained after intravenous
administration (almost 100%).
• The absorption of hydrophilic (polar) drugs occurs via the paracellular
route (between the epithelial cells via the tight junctions) and the
rate and extent of absorption is inversely proportional to the
molecular weight of the drug. Since the paracellular route provides a
much smaller area for absorption than the transcellular route (the
paracellular route comprises about 0.01% of the transcellular route in
the gastrointestinal tract), the absorption of hydrophilic compounds is
much slower than that of lipophilic drugs.

11. Formulation Factors Affecting
Intranasal Systemic Delivery
However, additional strategies can be employed to increase absorption across
the nasal epithelium. In essence, the bioavailability of nasally administered
drugs can be limited by:
• Low aqueous solubility.
• Rapid and extensive enzymatic degradation of the drug in the nasal cavity.
• Short contact time between the drug and the absorptive epithelium of the
turbinates due to mucociliary clearance
• Poor permeability of the drug across the respiratory epithelium.

12. Advantages And Disadvantages Of
Intranasal Drug Delivery For
Systemic Activity
Advantages Disadvantages
Large surface area for absorption (approximately
160 cm2).
Limited to small delivery volumes (25–200 µL)
therefore require potent drugs.
Good blood supply and lymphatic system. Mucociliary clearance, mucus barrier.
Avoids hepatic First-pass metabolism. Enzymatic activity (pseudo first-pass effect).
Epithelium is permeable to small, lipophilic drug
molecules; rapid absorption and onset of action.
Non-invasive, so minimal infection risk during
application and low risk of disease transmission
(unlike parenteral route).
Easy to sel -administer and adjust dose.