The nasal cavity is divided into two halves by the nasal septum and extends posterior to the nasopharynx, while the most anterior part of the nasal cavity, the nasal vestibule, opens to the face through the nostril. The nasal cavity constist three main region are nasal vestibule, olfactory region and respiratory region. The surface area in the nose can be enlarge about 150cm² by the lateral walls of the nasal cavity include a folded structure, it is very high surface area compared to its small volume. This folded structure consists of three turbinates, the superior, the median and the inferior. The main nasal airway having the narrow passage, usually it has 1-3mm wide and these narrow structures are useful to nose carryout it's main function.

The nasal cavity is covered with a mucous membrane which can be divided into two areas nonolfactory and olfactory epithelium, in this nonolfactory area include the nasal vestibules which is covered with skin like stratified squamous epithelium cells, where as respiratory region, which has typical airways epithelium covered with numerous microvill, resulting in a large surface area avalible for drug absorption and transport. in this way the mucous layer is propelled in a direction from the anterior to wards the posterior part of the nasal cavity. it secretes the mucous as mucus granules which are swelling in the nasal fluid to contribute to the mucus layer.

The mucus secretion is composed of about 95% water, 2 % mucin, 1% salts, 1% of other proteins such as al-bumin, immunoglobulin s, lysozyme and lactoferrin, and b 1% lipids. The mucus secretions gives immune protection against inhaled bacteria and virus. It also perform a number of physiological functions. It covered the mucosa, and physically and enzymatically protects it. the mucous has water holding capacity. It exhibits surface electrical activity⁶.

Mechanism of Nasal Absorption:

The initial step in the absorption of drug form nasal cavity is passage through the mucous larges or charged particle may find it more difficult to cross. But small uncharged particles easily passed through this layer, the mechanism for absorption through the nasal mucosa. This include particular transport via moment between cell and transcytosis by vesicle carries, transcelullar or simple diffusion across the membrane.

1. The first mechanism includes aqueous route of transport, which is also called as the paracellular route. This is slow and passive route, inverse log-log relationship between intranasal absorption and the molecular weight of water soluble compounds. Pooavailability was observed for drugs with a molecular weight greater than 1000 Daltons.

2. The second mechanism is transport a lipoidal route is known as transcellular process and is responsible for the transport of lipophilic drugs that show a rate dependency on their lipophilicity. Drugs also cross membrane by an active transport route via carrier mediated means or transport through the opening of junctions. For example, Chitosan, a natural biopolymer opens tight junctions between epithelial cells to facilitate drug transport.⁷

Drug Distribution and Deposition:

The distribution of drug delivery in transnaslly in the nasal cavity is one of the most important factor that could affect the efficiency of nasal absorption. Mode of administration also effect the distribution. Different type of administration are there, they are nose drops, plastic bottles nebulizer, An atomized pump, meterdose pressurized aerosols. Among this atomized pump deliver the drug effectivey than other dosage form. Nasal deposition of drug depends on the nasal resistance to airflow and the particle size. Partical with aerodynamic sizes 10-20um are often found to deposit on nasal mucosa. In the poorly absorbed regions like anterior atrium and posterior nasopharyngal region the deposition is poor. The deposition of aerosols also depends on partical size, density, shape, hygroscopicity of the particle. Presurlized gas propellant gives uniform distribution throughout the nasal mucosa. A meterdose delivery system gives a constant deposition rate³.

Physiochemical Property of Formulation:

1. PH:

The PH of the formulation, as well as that of nasal surface can affect a drugs permeation. To avoid nasal irritations, the ph of the nasal formulation should be adjusted to 4.5-6.5

2.Viscosity:

A higher viscosity of the formulation increases contact time between the drug and the nasal mucosa thereby increasing the time for permeation. At the same time highly viscous formulations interfere with the normal functions like ciliary beating or mucociliary clearance and thus alter the permeability of drugs.

3. Osmolarity:

Optimum osmolarity should maintain as it causes shrinkage of nasal epithelial mucosa and alter the permantion of drugs.

4. Buffer Capacity:

Nasal formulations are generally administered in small volume ranging from 25-20 µL. Hence, nasal secretions may alter the pH of the administrated dose. This can affects the concentration of unionized drug available for absorption. Therefore, an adequate formulation buffer capacity may be required to maintain the pH.

5. Drug Conversation, Dose and Dose Volume:

Drug concentration, dose and volume of administration are three interrelated parameters that impact the performance of the nasal delivery performance. Nasal absorption of L-Tyrosine was shown to increase with drug concentration in nasal perfusion experiments^(7).

Adavantage of Nasal Drug Delivery System:

1. Drug degradation that is observed in the gastrointestinal track in absent.

2. Hepatic first pass metabolism is avoided.

3. The nasal bioavailablty for smaller drug molecules is good.

4. Studies so far indicates that the nasal route is an alternative to parenteral route, especially for proteins and peptide drug.

5. Convenient for the patient especially for those on long term therapy, when compared with parenteral medication.

6. Polar compound exhibiting poor oral absorption may be particularly studies for this route of delivery.

7. Large nasal mucosa surface area for dose absorption.

8. Easy of administration, non-invasive.

9. Lower dose reduce side effects.

10. Self administration⁴

Limitations Nasal Drug Delivery System:

1. Delivery is expected to decreases with increasing molecular weight of drug.

2. Mucosal damages may occurs due to frequently use of intra nasal route.

3. Very specific amount i.e. 25-200µl can be delivered throw intra nasal route.

4. Ciliary movement after the drug permeability.

5. Difficult to administered drug in pathological condition such as nasal congestion due to cold or allergic reaction.

6. Some drug cannot administered throw this route because they causes nasal irritation.

7. There could be mechanical loss of dosages form into the other part of respiratory track like lungs because of the improper technique of administration.

8. The histological toxicity of different type of penetration enhancer used is not clearly known^(4).

Challenges and Opportunities for Nasal Drug Delivery System:

Existing nasal delivery device such as spray pumps and pipettes cannot fully exploit the describe potential advantage of nasal delivery. A large freaction of the dose is deposited on the anterior segment lined by skin, which is not the target for either topical drug or systemic drug. Drug transport along the floor of the nose may cause bad teste and irritation and reduce patient acceptance. Finally inadequate and variable deposition in the remote region housing the openings to the sinous and middle ears as well as the olfactory region, represent a real challenge for extended use of nasal administration of drug and vaccines. This applied in particular to the new advance and expensive drug requring demanding combination of reliable dosing, high patient compliance and reproducible bioability to ensure their efficincy and safty. Regarding actual formulation as liquid and delivered meter spray pumps. liquid formulation can be limited by the solubility, stability and dose volume. Powder, on the other hand, are more stable and it easier to customize the size and surface property. Some studies indicated reduce local irritations and more rapid absorption of powder. Bioactis has been developing nasal device, which are medical device that deliver drug to nose⁵

CONCLUSIONS:

Nasal drug delivery is apromising alternative route of drug administration for topical, systemic and central nervous system action. It has advantages in terms of reduces systemic exposure and hence side effects and avoiding first-pass metabolism. However, the intranasal route presents several limitations which must be overcome to develop a successful nasal medicine. Physiological conditions, physicochemical properties of drug and formulation are most important factors that affect nasal absorption. In future, the extensive research is necessary to make this route of delivery more efficient and popular⁸

REFERENCE:

1. Artical on review on nasal drug delivery system and it's contribution in therapeutical management by Sulaiman Alnasser published by International Journal of Pharmacy and Pharmaceutical Sciences refer page no.2455-3891 volume no 12 and issue 01, 2019

2. Article on recent technique in nasal drug delivery system by Parmar harshad, Bhandari Anand, Shah Dushyant published by International Journal of Drug Development and Research refer page no Anish Kumar D. et al. Review article on nasal drug delivery system,

3. Anish Kumar D. et al. Review article on nasal drug delivery system, International journal of Research in Pharmaceutical and Nano Science, 1(1), 2012,35-44.

4. Article on Nasal delivery of drug by Anupam Kr sachan, Swati Singh published by International Journal for Pharmaceutical Research Scholars, refer page no. 2277-7873, Volume no.03 and issue 10, 2014.

5. Artical on A review on factors affecting the design of nasal drug delivery system by Ram C. Dhakar, Sheo D. Maurya, Vijay K. Tilak, Anish K. Gupta, published by International Journal of Drug Delivery, refer page no. 0975-0215 and issue 10,2011.

6. Artical on Nasal drug delivery system-an overview by M.Alagusundaram, B.chengaiah K.Gnanaprakash, S.Ramkanth, C.Madhusudhana Chetty, D. Dhachinamoorthi, published by International Journal of Pharmascope, refer page no. 0975-7538 and volume no. 01 and issue on 2010.

7. Article on A Recent review on nasal drug delivery system by Jayesh K. Kakad, Prasad K. More, Sheetal B. Gondkar, Ravindranath B. Saudagar, published by word Journal of Pharmaceutical Research, refer page no. 2277-7105 and volume no. 04 and issue on 15, 2014

8. Article on Nasal drug delivery: An approach of drug delivery through nasal route by Sanjay Dey, Beduin Mahanti, Bhaskar Mazumder, Ananaya Malgope, Sandeepan Desgupata. Published by Pelagia Research Library, refer page no. 0976-8688 and issue on 01,2014

Received on 10.06.2021 Modified on 29.06.2021

Asian J. Pharm. Tech. 2021; 11(4):289-292.

DOI: 10.52711/2231-5713.2021.00048