This document discusses drug delivery through the nasal route. It provides background on the nasal route's potential for administering drugs that are susceptible to degradation or first-pass metabolism. The nasal cavity offers rapid drug absorption and onset of action while avoiding issues with intravenous delivery. Key factors that influence nasal drug delivery include drug properties, formulation properties like pH and viscosity, and physiological barriers like mucociliary clearance and enzymatic degradation. Successful nasal delivery may require absorption enhancers to improve permeability or bioadhesive polymers to increase residence time in the nasal cavity.
Pulmonary route used to treat different respiratory diseases from last decade.
The inhalation therapies involved the use of leaves from plants, vapours from aromatic plants, balsams, and myhrr.
Pulmonary drug delivery is primarily used to treat conditions of the airways, delivering locally acting drugs directly to their site of action.
Delivery of drugs directly to their site of action reduces the dose needed to produce a pharmacological effect.
Pulmonary route used to treat different respiratory diseases from last decade.
The inhalation therapies involved the use of leaves from plants, vapours from aromatic plants, balsams, and myhrr.
Pulmonary drug delivery is primarily used to treat conditions of the airways, delivering locally acting drugs directly to their site of action.
Delivery of drugs directly to their site of action reduces the dose needed to produce a pharmacological effect.
Introduction
Anatomy and physiology of lungs
Advantage and disadvantage of Pulmonary Drug Delivery system.
Aerosols , propellants & container types.
Current technologies for pulmonary drug delivery.
New technologies for pulmonary drug delivery.
Evaluation of Pharmaceutical Aerosols & PDDS.
Pulmonary drug delivery is primarily used to treat conditions of the airways, delivering locally acting drugs directly to their site of action.
Delivery of anti-asthmatic and other locally acting drugs directly to their site of action reduces the dose needed to produce a pharmacological effect, while the low concentrations in the systemic circulation may also reduce side-effects.
The drugs which are administered by pulmonary route are not only for lungs delivery but it goes to systemic circulation and produce the effect where it is desired through out the body. For Eg. A product containing ergotamine tartrate is available as an aerosolized dosage inhaler for the treatment of migraine & Volatile anesthetics, including, halothane, are also given via the pulmonary route.
Used for inhalation and topical aerosols .
Manufactured by impact extrusion process.
Light in weight, less fragile, Less incompatibility due to its seamless nature.
Greater resistance to corrosion .
Pure water and pure ethanol cause corrosion to Al containers.
Added resistance can be obtained by coating inside of the container with organic coating like phenolic , vinyl or epoxy and polyamide resins.
Nose to brain a versatile mode of drug delivery systemSagar Savale
The Aim of present review highlights transport of drug in nose to brain via olfactory and trigeminal nerve pathway by passing blood brain barrier (BBB). Nose to brain drug delivery has received a great deal of attention as a non-invasive, convenient and reliable drug delivery system for the systemic and targeted administration of drugs.
Statistical modeling in pharmaceutical research and developmentPV. Viji
Statistical modeling in pharmaceutical research and development , Statistical Modeling , Descriptive Versus Mechanistic Modeling , Statistical Parameters Estimation , Confidence Regions , Non Linearity at the Optimum , Sensitivity Analysis , Optimal Design , Population Modeling
Hi, Intranasal drug delivery to brain is one of the amazing drug delivery systems..........
Here we can deliver even the hydrophillic drugs to brain.........
through the first and fifth cranial nerves...........
thanking you,,
Introduction
Anatomy and physiology of lungs
Advantage and disadvantage of Pulmonary Drug Delivery system.
Aerosols , propellants & container types.
Current technologies for pulmonary drug delivery.
New technologies for pulmonary drug delivery.
Evaluation of Pharmaceutical Aerosols & PDDS.
Pulmonary drug delivery is primarily used to treat conditions of the airways, delivering locally acting drugs directly to their site of action.
Delivery of anti-asthmatic and other locally acting drugs directly to their site of action reduces the dose needed to produce a pharmacological effect, while the low concentrations in the systemic circulation may also reduce side-effects.
The drugs which are administered by pulmonary route are not only for lungs delivery but it goes to systemic circulation and produce the effect where it is desired through out the body. For Eg. A product containing ergotamine tartrate is available as an aerosolized dosage inhaler for the treatment of migraine & Volatile anesthetics, including, halothane, are also given via the pulmonary route.
Used for inhalation and topical aerosols .
Manufactured by impact extrusion process.
Light in weight, less fragile, Less incompatibility due to its seamless nature.
Greater resistance to corrosion .
Pure water and pure ethanol cause corrosion to Al containers.
Added resistance can be obtained by coating inside of the container with organic coating like phenolic , vinyl or epoxy and polyamide resins.
Nose to brain a versatile mode of drug delivery systemSagar Savale
The Aim of present review highlights transport of drug in nose to brain via olfactory and trigeminal nerve pathway by passing blood brain barrier (BBB). Nose to brain drug delivery has received a great deal of attention as a non-invasive, convenient and reliable drug delivery system for the systemic and targeted administration of drugs.
Statistical modeling in pharmaceutical research and developmentPV. Viji
Statistical modeling in pharmaceutical research and development , Statistical Modeling , Descriptive Versus Mechanistic Modeling , Statistical Parameters Estimation , Confidence Regions , Non Linearity at the Optimum , Sensitivity Analysis , Optimal Design , Population Modeling
Hi, Intranasal drug delivery to brain is one of the amazing drug delivery systems..........
Here we can deliver even the hydrophillic drugs to brain.........
through the first and fifth cranial nerves...........
thanking you,,
Introduction to Nasal drug delivery system,Anatomy of Nasal cavity,Advantages n limitataions of Nasal DDS,Mechanism,factors affecting Nasal DDS,Formulation,methods to enhance Nasal DDS,Dosage forms,Evalaution
The use of the nasal route for the delivery of challenging drugs such as small polar molecules, vaccines, hormones, peptides and proteins has created much interest in nowadays. Due to the high permeability, high vasculature, low enzymatic environment of nasal cavity and avoidance of hepatic first pass metabolism are well suitable for Systemic delivery of drug molecule via nose Many drug delivery devices for nasal application of liquid, semisolid and solid formulation are investigated to deliver the drugs to the treat most crisis CNS diseases i.e., Parkinson’s dis ease, Alzheimer’s disease because it requires rapid and or specific targeting of drugs to the brain. It is well suitable for the delivery of biotechnological products like proteins, peptides, hormones, DNA plasmids for DNA vaccines to give enhanced bioavailability. This review sets out to discuss some factors affecting nasal absorption, bioavailability barriers, strategies to improve nasal absorption, new developments in nasal dosage form design and applications of nasal drug delivery system. Aarti C. Nangare | Sujit Kakade | Ashok Bhosale "Nasal Drug Delivery System: A Review" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-5 | Issue-5 , August 2021, URL: https://www.ijtsrd.com/papers/ijtsrd43868.pdf Paper URL: https://www.ijtsrd.com/pharmacy/pharmacy-practice/43868/nasal-drug-delivery-system-a-review/aarti-c-nangare
In ancient time Ayurvedic system of medicine used nasal route for administration of drugs and the process is called as “Nasya”.
Nasal route has been used for local effects of decongestants but, in recent time it is being considered as a preferred route of drug delivery for systemic bioavailability.
Various proteins & peptides have shown a good bioavailability through this route.
Pulmonary drug delivery system M.pharm -2nd sem P'ceuticssakshisoni2385
M.pharm Pharmaceutics 2nd sem.
introduction to Pulmonary drug delivery system, mechanism, Aersools, and aerosol parts barriers, physiological properties, preparation methods, evaluation parameters, advantages and diadvantages.
Targeted drug delivery to the respiratory system- An article Satyaki Mishra
This is an article (preview) on Pulmonary drug delivery system written for partial submission of Post-graduation assignment.. The study further helps in enhancing knowledge on target specific drug delivery system. If this article is of any help to you, kindly consider downloading it. You can drop your mail id in the comment section.
Different Variable and Recent Development in Noval Buccal Drug Delivery Systemijtsrd
The buccal region of the oral cavity is an attractive target for administration of the drug of choice, particularly in overcoming deficiencies associated with the latter mode of administration. Problems such as high first pass metabolism and drug degradation in the gastrointestinal environment can be circumvented by administering the drug via the buccal route. Moreover, rapid onset of action can be achieved relative to the oral route and the formulation can be removed if therapy is required to be discontinued. It is also possible to administer drugs to patients who unconscious and less co operative. To prevent accidental swallowing of drugs adhesive mucosal dosage forms were suggested for oral delivery, which included adhesive tablets, adhesive gels, adhesive patches and many other dosage forms with various combinations of polymers, absorption enhancers. Natural polymers have recently gained importance in pharmaceutical field. Mucoadhesive polymers are used to improve drug delivery by enhancing the dosage form's contact time and residence time with the mucous membranes. Mucoadhesion may be defined as the process where polymers attach to biological substrate or a synthetic or natural macromolecule, to mucus or an epithelial surface. When the biological substrate is attached to a mucosal layer then this phenomenon is known as mucoadhesion. The substrate possessing bioadhesive polymer can help in drug delivery for a prolonged period of time at a specific delivery site. The studies of Mucoadhesive polymers provide a good approach of mucoadhesion and some factors which have the ability to affect the mucoadhesive properties of a polymer. Both natural and synthetic polymers are used for the preparation of mucoadhesive buccal patches. In addition to this, studies have been conducted on the development of controlled or slow release delivery systems for systemic and local therapy of diseases in the oral cavity. Deepak Chandra Sharma | Pranshu Tangri | Sunil Jawla | Ravinesh Mishra "Different Variable and Recent Development in Noval Buccal Drug Delivery System" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-3 | Issue-5 , August 2019, URL: https://www.ijtsrd.com/papers/ijtsrd18934.pdfPaper URL: https://www.ijtsrd.com/pharmacy/novel-drug-delivery-sys/18934/different-variable-and-recent-development-in-noval-buccal-drug-delivery-system/deepak-chandra-sharma
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Hemodialysis: Chapter 3, Dialysis Water Unit - Dr.Gawad
Brain targeted drug delivery through nasal route
1. BRAIN TARGETED DRUG DELIVERY THROUGH
NASAL ROUTE
GUIDED BY:
DR. DHAIVAT PARIKH
PHARMACEUTICAL TECHNOLOGY & BIOPHARMACEUTICS
PREPARED BY:
ISHANI PANDIT (14MPH109)
PHARMACEUTICAL TECHNOLOGY & BIOPHARMACEUTICS 3/1/2015 1
2. CONTENT
Introduction
Rational for nose to brain delivery
Anatomy of nose
Barriers for nasal delivery
Mechanism of Drug absorption
Blood supply to nasal cavity
Crucial factors for nasal formulation
Advantages & Disadvantages
Applications
Nasal drug products for systemic drug delivery in market
Conclusion 3/1/2015 2
3. INTRODUCTION
Drug delivery through nasal route has been potentially explored as an alternative route for the
administration of vaccines and biomolecules such as proteins, peptides and non-peptide drugs that
are susceptible to enzymatic or acidic degradation and first-pass hepatic metabolism.
The nasal mucosa is one of the most permeable and highly vascularized site for drug administration
ensuring rapid absorption and onset of therapeutic action.
In addition it minimizes the lag time associated with oral drug delivery and offers noninvasiveness,
self medication, patient comfort and patient compliance which are hurdled in intravenous drug
therapy.
3/1/2015 3
4. RATIONALE OF NOSE TO BRAIN DELIVERY
Currently, Nasal drug delivery has been recognized as a very promising route for delivery of
therapeutic compounds including biopharmaceuticals.
Nasal administration is a logical choice for topical nasal treatments such as antihistamines and
corticosteroids. The nasal mucosa has also received attention as a viable means of systemic
administration of analgesics, sedatives, hormones, cardiovascular drugs, and vaccines.
Conventionally, the nasal route has been used for local delivery of drugs for treating nasal allergy,
nasal congestion, or nasal infections.
However systemic delivery through the nasal route has recently begun to explore possibilities for
those requiring a rapid onset of action or necessitating avoidance of severe proteolysis involved in
oral administration (e.g., most peptide and protein drugs).
Successful attempts to deliver corticosteroid hormones through the nasal route for systemic
absorption3 have triggered further studies in this area. 3/1/2015 4
5. ANATOMY & PHYSIOLOGY OF NASAL CAVITY
The human nose is divided by the median septum, a central partition of bone and cartilage; each
symmetrical half opens at the face via the nostrils and connects with the mouth at the nasopharynx.
The nasal vestibule, the respiratory region and the olfactory region are the three main regions of the
nasal cavity.
The lateral walls of the The sub mucosal zone of the nasal passage is extremely vascular and this
network of veins drains blood from the nasal mucosa directly to the systemic circulation, thus
avoiding first-pass metabolism.
the nasal cavity is covered with a mucous membrane which can be divided into non-olfactory and
olfactory epithelium areas. The non-olfactory area includes the nasal vestibule, which is lined with
skin-like cells and respiratory region. About 15–20% of the respiratory cells are covered with a layer of
long cilia, which move in a coordinated way to propel mucus towards the pharynx. 3/1/2015 5
6. CONTINUE…
nasal cavity include a folded structure which enlarges the surface area in the nose to about 150
cm2.17 This folded structure includes three turbinates. The superior, the median and the inferior.
In the main nasal airway, the passages are narrow, normally only 1–3 mm wide and this narrow
structure enables the nose to carry out its main functions.
During inspiration, the air comes into close contact with the nasal mucosa and particles such as dust
and bacteria are trapped in the mucus. Additionally, the inhaled air is warmed and moistened as it
passes over the mucosa. This conditioning of the inhaled air is facilitated by the fluid secreted by the
mucosa and the high blood supply in the nasal epithelium. 17-18
3/1/2015 6
7. CONTINUE…
Respiratory epithelium &mucociliary clearance:
It composed of four types of cells:
Non-ciliated
Ciliated columnar cell
Basal cell
Goblet cell
This cell prevent drying of mucosa by trapping moisture. These cell facilitated active transport
processes such as exchange of water & ions between cell & motility of cilia.about 15-20% of
respiratory cells covered with layer of lomg cilia. Mucus present over epithelial cell causes mucociliary
clearance. Mucous moves only in one direction from the anterior to posterior part of nasal cavity to
the nasopharynx. Mucous secretion gives immune protection against inhaled bacteria or virus.
Mucous has water holding capacity, it exhibit surface electrical activity, it also act as transport &
adhesive for particulate matter towards nasopharynx.
3/1/2015 7
8. CONTINUE…
Olfactory region:
In human olfactory region is located on the roof of the nasal cavities, just below the cribriform plate of
the Ethmoid bone, which separates the nasal cavities from the cranial cavity22. The olfactory
epithelium predominantly contain three cell types: 1. Olfactory neural cells, 2. Sustenticular
(supporting) cells, 3. The basal cells.
3/1/2015 8
10. BARRIERS FOR NASAL DELIVERY
1. Low Bioavailability
Bioavailability of polar drugs is generally low, about 10% for low molecular weight drugs and not
above 1% for peptides such as calcitonin and insulin.
The most important factor limiting the nasal absorption of polar drugs and especially large molecular
weight polar drugs such as peptides and proteins are the low membrane permeability.
Drugs can cross the epithelial cell membrane either by the transcellular route or vesicular transport
mechanisms or by the paracellular route. Polar drugs with molecular weights below 1000 Da will
generally pass the membrane using the latter route.
3/1/2015 10
11. CONTINUE…
Nasal absorption of such polar drugs can be greatly improved by co administration of absorption
enhancing agents.
Agents generally used for transnasal absorption includes surfactants (laureth-9, sodium laurylsulfate),
bile salts ,bile salt derivatives (sodium glycocholate, sodium deoxycholate, sodium
taurodihydrofusidate), fatty acids,fatty acid derivatives (linoleic acid), phospholipids
(lysophosphatidylcholine), various cyclodextrins and cationic compounds like chitosan and its
derivatives, poly-L-arginine, poly-L- lysine.
These enhancers work by a variety of mechanisms but generally they act by altering the permeability
of the epithelial cell layer by modifying the phospholipid bilayers, leaching of proteins from the
membrane or even stripping off the outer layer of the mucosa
3/1/2015 11
12. CONTINUE…
2. Mucocilliary clearance
The general fast clearance of the administered formulation from the nasal cavity due to the
mucociliary clearance mechanism is another factor of importance for low membrane transport. This is
especially the case when the drug is not absorbed rapidly enough across the nasal mucosa. It has
been shown that for both liquid and powder formulations, which are not bioadhesive, the half life for
clearance is of the order of 15 - 30 min.
The use of bioadhesive excipients in the formulations is an approach to overcome the rapid
mucociliary clearance.
The clearance may also be reduced by depositing the formulation in the anterior, less ciliated part of
the nasal cavity thus leading to improved absorption 3/1/2015 12
13. CONTINUE…
3. Enzymatic Degradation
Another contributing, but often less considered factor to the low bioavailability of peptides and
proteins across the nasal mucosa is the possibility of an enzymatic degradation of the molecule in the
lumen of the nasal cavity or during passage through the epithelial barrier. These sites both contain
exo-peptidases such as mono and diaminopeptidases that can cleave peptides at their N and C
terminals and endo-peptidases such as serine and cysteine, which can attack internal peptide bonds.
3/1/2015 13
14. MECHANISM OF DRUG ABSORPTION THROUGH NOSE
The first step in the absorption of drug from the nasal cavity is passage through the mucus. Small
unchanged particles easily pass through this layer. However, large or charged particles may find it
more difficult to cross.
Subsequent to a drug’s passage through the mucus, there are several mechanisms for absorption
through the mucosa.
These include transcellular or simple diffusion across the membrane, paracellular transport via
movement between cell and transcytosis by vesicle carriers.
Obstacles to drug absorption are potential metabolism before reaching the systemic circulation and
limited residence time in the cavity. Several mechanisms have been proposed but the following two
mechanisms have been considered predominantly.
3/1/2015 14
15. CONTINUE…
The first mechanism involves an aqueous route of transport, which is also known as the paracellular
route. This route is slow and passive. There is an inverse log-log correlation between intranasal
absorption and the molecular weight of water-soluble compounds. Poor bio-availability was observed
for drugs with a molecular weight greater than 1000 Daltons.
The second mechanism involves transport through a lipoidal route that is also known as the
transcellular process and is responsible for the transport of lipophilic drugs that show a rate
dependency on their lipophilicity. Drugs also cross cell membranes by an active transport route via
carrier-mediated means or transport through the opening of tight junctions.38 For example, Chitosan,
a natural biopolymer opens tight junctions between epithelial cells to facilitate drug transport.
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16. BLOOD SUPPLY TO NASAL CAVITY
Nasal vasculature is richly supplied with blood to fulfil the basic functions of nasal cavity such as
heating and humidification, olfaction, mucociliary clearance and immunological functions. Blood
supply comes from the branches of both the internal and external carotid artery, including branches
of the facial artery and maxillary artery.
The name arteries of nose are:
Sphenopalatine artery
Anterior Ethmoidal Artery
Facial Artery
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17. NOSE TO BRAIN DELIVERY
The olfactory region is a small patch of tissue containing small receptor and is located at the very top
of the nasal cavity near the inner end of the upper throat.
The patch has a yellowish tinge in contrast to its surrounding pink tissue and consists of several million
tiny endings of the olfactory nerve whose bundle passes through the cribiform plate and enters the
fastest forward extension of brain.
Olfactory epithelium is known to be a portal of entry of the substance into the central nervous system
and peripheral circulation.
The transport of the drug across the nasal membrane and into the bloodstream may involve the
passive diffusion of drug through the pores in the nasal mucosa and some from non passive transport.
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20. CRUCIAL FACTORS FOR NASAL FORMULATIONS
Factors related to drug:
I. Lipophilicity: Absorption of drug substance through biological membrane may be dependent on hydrophilic
lipophilic balance of the compound. On increasing lipophilicity, the nasal absoption of the compound normally
increases. Lipophilic compounds tend to readily cross biological membranes via the transcellular route since
they are able to partition into the lipid (bilayer) of the cell membrane and diffuse into and traverse the cell in
the cell cytoplasm. Nasal absorption of steroids was directly correlated with lipophillicity of drug
molecules and was found to be independent of pH.
II. Partition coefficient & pKa: According to the pH partition theory, unionized form of drug are well absorbed
compared with ionized form of drug and the same theory is applicable in the case of nasal drug absorption.
III. Chemical form: The chemical form of a drug is important in determining absorption.
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21. CONTINUE…
IV. Molecular weight: A linear inverse correlation has been reported between the absorption of drugs and
molecular weight up to 300 Daltons. Absorption decreases significantly if the molecular weight is greater than
1,000 Daltons except with the use of absorption enhancers.
V. Particle size: It has been reported that particles greater than 10 µm in size are deposited in the nasal cavity.
Particles that are 2 to 10µm can be retained in the lungs and particles of less than 1 µm are inhaled.
VI. Solubility & Dissolution rate: Drug solubility and dissolution rates are important biopharmaceutical factors50
in determining nasal absorption from powders and suspensions. The particles deposited in the nasal cavity need
to dissolve prior to absorption. The fluid available for dissolution of drug particles in nasal cavity or mucosa is
very less when compared to the gastrointestinal fluid in oral drug delivery.51 saturation solubility of drug in a
given nasal physiological pH is very important parameter, which determines the rate and extent absorption of
nasal dosage form
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22. FORMULATION FACTORS:
I. pH of formulation: Both the pH of the nasal cavity and pKa of a particular drug need to be considered
to rationalize systemic absorption. Nasal irritation is minimized when products are delivered with a pH ranging
between 4.5 and 6.5. The pH of a nasal formulation is important for the following reasons:
o To avoid irritation of nasal mucosa.
o To allow the drug to be available in unionized form for absorption.
o To prevent growth of pathogenic bacteria in the nasal passage.
o To maintain functionality of excipients such as preservatives.
o To sustain normal physiological ciliary movement .
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23. CONTINUE…
II. Osmolarity: Drug absorption can be affected by tonicity of the formulation. Hypertonic saline solutions are
also known to inhibit or cease ciliary activity. Low pH has a similar effect on cells as hypertonic solutions.
III. Gelling agents: Retention of the nasal formulation in the nasal cavity can enhance therapeutic effect by
virtue of enhancing rate and extent of drug absorption. increasing the viscosity may provide a means of
prolonging the effect of nasal formulation.
IV. Solubilizers : The aqueous solubility of a drug is always a limitation for nasal drug delivery in solution.
Conventional solvents or co-solvents such as glycols, small quantities of alcohol, Transcutol (diethylene glycol
monoethyl ether), medium chain glycerides and Labrasol (saturated polyglycolyzed C8-C10 glyceride) can be
used to enhance the solubility of drugs. Other options include the use of surfactants or cyclodextrins such as
hydroxypropyl-beta-cyclodextrin that serve as biocompatible solubilizers and stabilizers in combination with
lipophilic absorption enhancers. In such cases, impact of the solubilizers on nasal irritancy should be considered.
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24. CONTINUE…
V. Drug concentration, required dose, and dose volume: Drug concentration, dose and volume
of administration are three interrelated parameters that impact the performance of the nasal delivery system. .
Ex vivo experiments in rats demonstrated the effect of drug concentration on nasal drug absorption.
VI. ROLE OF ABSORPTION ENHANCERS: The selection of absorption enhancers is based upon their
acceptability by regulatory agencies and their impact on nasal physiological function. Absorption enhancers may
be required when a drug exhibits poor membrane permeability, large molecular size, lack of lipophilicity and
susceptibility to enzymatic degradation by aminopeptidases. Generally, the absorption enhancers act via one of
the following mechanisms:
o Inhibit enzyme activity
o Reduce mucus viscosity or elasticity
o Decrease mucociliary clearance
o Open tight junctions; and
o Solubilize or stabilize the drug
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25. PHYSIOLOGICAL FACTORS
I. Effect of deposition on absorption: Deposition of formulation in the anterior portion of the
nose provides a longer nasal residence time and better absorption. The dosage form deposited in
posterior chamber of nasal cavity will be eliminated by nasal mucocilliary clearance and hence show
low bioavailability. The site of deposition and deposition pattern of liquid dosage form is dependent
on the delivery device, mode of administration, physicochemical properties of drug molecule.
I. Nasal blood flow: The nasal mucosal membrane is very rich in vasculature and plays a vital role
in the thermal regulation and humidification of inhaled air. Drug absorption will depend upon the
vasoconstriction and vasodilatation of these blood vessels.
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26. CONTINUE…
IV. Effect of mucociliary clearance: It is important that the integrity of the nasal clearance
mechanism is maintained to perform normal physiological functions such as the removal of dust,
allergens and bacteria. The absorption of drugs is influenced by the residence time between the drug
and the epithelial tissue. The mucociliary clearance is inversely related to the residence time and
therefore inversely proportional to the absorption of drugs administered.
V. Effect of enzymatic activity: Several enzymes that are present in the nasal mucosa might
affect the stability of drugs. For example, proteins and peptides are subjected to degradation by
proteases and amino-peptidase at the mucosal membrane.
VI. Effect of pathological condition: Intranasal pathologies such as allergic rhinitis, infections, or
previous nasal surgery may affect the nasal mucociliary transport process and/or capacity for nasal
absorption. During the common cold, the efficiency of an intranasal medication is often
compromised.
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27. ADVANTAGE OF NASAL DRUG DELIVERY SYSTEM
Large nasal mucosal surface area for dose absorption
Rapid drug absorption via highly vascularized mucosa
Rapid onset of action
Ease of administration, noninvasive
By pass the BBB
Avoidance of the gastrointestinal tract and first pass metabolism
Improved Bioavailability
Direct transport into systemic circulation and CNS is possible
Lower dose/reduced side effects
Improved convenience and compliance
Self-administration
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28. DISADVANTAGES
Volume that can be delivered into nasal cavity is restricted to 25-200 μl.
Not feasible for high molecular weight more than 1k Da
Adversely affected by pathological conditions
Drug permeability may alter due to ciliary movement
Drug permeability is limited due to enzymatic inhibition
Nasal irritants drugs cannot be administered through this route
Exact mechanism is not yet clearly known
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29. APPLICATIONS OF NASAL DRUG DELIVERY SYSTEM
I. Delivery of Vaccines through Nasal Route:
o 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 defence system:
o Main reasons for exploiting the nasal route for vaccine delivery.
o The nasal passages are rich in lymphoid tissue.
o Creation of both mucosal and systemic immune responses.
o Low cost, patient compliance, non-injectable and safe
o The feasibility of the nasal route for administering vaccines against plague, diphtheria tetanus,
influenza, cholera, and HIV has already been tested for inducing both mucosal and systemic immune
response against the carried antigen. 3/1/2015 29
30. CONTINUE…
II. Nose to Brain drug delivery system :
o The success of cell based therapy for
neurodegenerative disorders depend on
therapeutic properties of the cell type, on the
method and safety of administration, on the
amount of cells delivered to the site of injury
and finally on the avoidence of excessive
incorporation of the therapeutic cell into other
organ and system.
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31. CONTINUE…
In this, methodologically transplantation may raise problem not only because of
grapht rejection as a result of immunological response to the transplant. The
intranasal administration of mesenchyamal stem cells and glioma cells to the brain of
rodent and the enhancement of cell delivery with hyaluronidase. This biological
pathway of cell migration from the nasal mucosa to the brain thus provide an
opportunity for development of cell delivery method for therapeutic and
experimental use in treating brain tumour model.
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32. CONTINUE…
III. Rapid delivery of Metoclopramide Hydrochloride: It is potent anti-emetic effective in
the treatment and vomiting associated with migraine, cancer therapy, pregnancy. It is well absorb
orally and shows peak plasma concentration in 1 to 2 hours after oral dose. But due to first pass
metabolism of metoclopramide hydrochloride its plasma concentration and bioavailability showing
variable values between 32% to 98%. In this study nasal formulation of metoclopramide
hydrochloride were developed to increase the extent of absorption through bypassing of hepatic first
pass metabolism and to develop alternative antiemetic therapy. Nasal bioavailability of this drug may
be improved aid of absorption promoters which include anionic enhancers such as bile salt as well as
new cationic enhancers such as chitosan, protamine and poly-L-arginine.The highest promoting effect
was observed with the bile salt sodium, deoxycholate where about 92% of the drug was absorb in 25
min. from the rat nasal cavity and the Kapp showed more than two fold increase as compare to
controlled (from 0.045 to 0.1017 min-1) 3/1/2015 32
33. CONTINUE…
IV. Insulin like growth factor-I (IGF-I): Intranasal administration is a non-invasive method of
bypassing the BBB and delivers IGF-I to the brain directly from nasal cavity along the pathway that
seems to be associated with the peripheral olfactory and trigeminal system.IGF-I has been proposed
as a treatment for stroke. However, it does not efficiently cross the BBB. Intracerebroventricular
injection of IGF-I has been shown to offers protection against cerebral ischemic damage in rats
although this invasive method may not be practical in humans. Treatment of middle cerebral artery
occlusion (MCAO).treatment was initiated 10 minute after the onset of MCAO and then again 24 hrs.
And 48 hrs. Later. Intranasal dosing of 75µg IGF-I(225µg total IGF-I over 48hours) significantly
reduced corrected infarct volume by 60% Vs. control (P< 0.001) and hemispheric swelling by 45.6%
Vs. control(P<0.05).neurologic function assessed by the postural reflex, flexor response and adhesive
tape test was also improved by intranasal IGF-I as compared to control. 3/1/2015 33
34. CONTINUE…
V. Intranasal Insulin delivery: The oral route is preferred for administration of drug, particularly
those required in chronic therapy, it is not feasible for the systemic delivery of most peptide and
protein drugs including insulin. Due to the poor oral availability insulin is now a days administered
parenterally. There are numorous disadvantages to injectable insulin therapy. The difficulties in
achieving normal physiological profile of insulin by injectable therapy has led to the investigation of
alternative, non-parenteral, route for the delivery of insulin in an attempt to improve glycemic
control. There are number of other non- parenteral route other than oral route which have been
investigated for the systemic administration of peptide and protein drug such as transdermal, ocular,
buccal, rectal, vaginal, pulmonary and nasal route. Out of all this route intranasal route is more viable
and effective.
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35. CONTINUE…
Sephadex (dextran microsphere)was shown to promote nasal insulin absorption in rats, although
DEAE-sephadex(DEAE- dextran microsphere)was ineffective which correlated with the in vitro release
characteristic of insulin from microsphere system.dextran microsphere which were coated with insulin
were shown to be more effective in terms of promoting insulin absorption in rats than insulin-loaded
microsphere. By using chitosan polymer as absorption enhancer the different percentage of chitosan
is used for making formulation for intranasal administration.0.5%and 1.5%chitosan was used this
shows increase in bioavailability through intranasal administration of insulin.
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36. NASAL FORMULATIONS
The deposition and deposition area are mainly a function of the delivery system and delivery device.
Different dosage forms and their application to deliver the drugs to the central nervous system
following intranasal drug delivery are discussed in this section.
LIQUID DOSAGE FORMS
Liquid dosage forms either in form of soluble, suspended or colloidal systems are normally used for
formulating nasal delivery systems.
Nasal sprays: Both solution and suspension formulations can be formulated into nasal sprays. Due
to the availability of metered dose pumps and actuators, a nasal spray can deliver an exact dose
anywhere from 25 to 200 µL. The particle size and morphology (for suspensions) of the drug and
viscosity of the formulation determine the choice of pump and actuator assembly. Solution and
suspension sprays are preferred over powder sprays because powder results in mucosal irritation.3/1/2015 36
37. CONTINUE…
Nasal emulsions, microemulsions and nanoparticles: Intranasal emulsions and
nanoparticles have not been studied as extensively as other liquid nasal delivery systems. Nasal
emulsions offer the advantages for local application mainly due to the viscosity. One of the major
disadvantages is poor patient acceptability. The physical stability of emulsion formulations and precise
delivery are some of the main formulation issues.
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38. CONTINUE…
SEMI-SOLID DOSAGE FORMS:
Semi-solid systems, for example gels, ointments and liquid systems containing polymers that gel at
particular pH changes are usually employed for designing the nasal drug delivery systems.
Nasal gels Nasal gels are thickened solutions or suspensions, of high- viscosity. The advantages of a
nasal gel include the reduction of post-nasal dripping due to its high viscosity, reduction of the 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 the mucosa for better
absorption.67 Vitamin B12 and apomorphine gel have been successfully employed to achieve desired
therapeutic concentrations following nasal administration.
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39. CONTINUE…
SOLID DOSAGE FORMS:
Solid dosage forms are also becoming popular for intranasal drug delivery, although these
formulations are more suitable for pulmonary drug delivery and similar applications, since it can cover
the vasculature within the epithelium of nasal mucosa.
Nasal powders: Powder dosage forms may be developed if solution and suspension dosage forms
cannot be developed, mainly due to lack of drug stability. The advantages of nasal powder dosage
form are the absence of preservative and superior stability of the drug in the formulation. However,
the suitability of the powder formulation is dependent on the solubility, particle size, aerodynamic
properties and nasal irritancy of the active drug and/or excipients. An additional advantage of this
system is local application of drug, but nasal mucosa irritancy and metered dose delivery are some of
the challenges for formulation scientists and device manufacturers who are interested in powder
dosage forms. 3/1/2015 39
40. NEEDS AND FUTURE PROSPECTIVES OF NASAL DRUG DELIVERY
In the field of drug delivery, drug delivery technologies will play a key role in the success of the
industry. The need for non-invasive drug delivery systems continues due to poor acceptance and
compliance with the existing delivery systems. The current needs of the industry are improved
solubility/stability, biological half-life and bioavailability enhancement of poorly absorbed drugs. Key
issues facing the biopharma industry are to improve safety, improve efficacy for organ targeting, and
improved compliance via sustained release or increasing residence time of drug at the site of
application.
New technologies include improved nasal formulations; site specific release, carrier- based systems,
advanced spray formulations, atomized mist technology, preservative free system and integrated
formulation development are strictly needed for success of drug delivery through nasal mucosa. For
success of nasal drug delivery Researchers has to on: 3/1/2015 40
41. CONTINUE…
Development of delivery technologies to increase efficacy and reduce side effects by target delivery
with variations potential of the drug.
Development of new technologies to deliver macromolecules with utilization of biotechnology and
high technology.
Development of integrated/improved nasal formulations.
Development of integrated device development for successful delivery of therapeutics.
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42. CONCLUSION
Drug delivery through nasal route provides a practical, non invasive method of by passing the blood
brain barrier (BBB) in order to deliver therapeutic agents to the brain. This method allows drugs that
do not cross the BBB to be delivered to the central nervous system in a few minutes along with both
the olfactory and trigeminal neuronal pathway.
This delivery system has clinical benefits like reduction in drug dosage and systemic exposure, which
results in lesser side effects. It is expected that nasal drug formulations will continue reach to the
market and this delivery will include not only drugs for acute and chronic disease but also novel nasal
vaccines for local or systemic protection against microbial infection. However it is well known that
intranasal route has several limitations which must be overcome to develop a successful nasal
formulation.
Drug related factor and pathophysiological condition of nose determine the nasal drug absorption.
Some common approaches, like increasing the nasal residence time of drug, use of absorption or
penetration enhancers and minimization of the mucociliary clearance, enhances the bioavailability of
nasally administered drug.
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43. CONTINUE…
This route is believed to be an alternative route to oral and parenteral because of the successful
administration of vaccines and biomolecules such as proteins, peptides and non-peptide drugs, that
are susceptible to enzymatic or acidic degradation and first-pass hepatic metabolism .Moreover it
also offers noninvasiveness, self medication, patient comfort and patient compliance which are
hurdled in intravenous drug therapy
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44. REFERENCES
Arun Kumar Singh et al; “Nasal Cavity: a promising transmucosal platform for drug delivery and
research approaches from nasal to brain targeting ”, Journal of Drug Delivery & Therapeutics; 2012,
2(3): 22-33.
Choudhary Rakhi et al; “Nasal route: A Novelestic Approch for Targeted Drug Delivery to CNS”,
International research Journal of Pharmacy, 2013, 4(3).
Kapil Kulkarni et al; “Brain Targetting through Intranasal Route”, International Journal of PharmTech
Research, Vol.5, No.4, pp 1441-1450, Oct-Dec 2013.
Daljeet Sharma et al; “Drug Targeting to Brain : A Review”, International Journal of Pharmaceutical
Research and Development, 2011/PUB/ARTI/VOV-3/ISSUE-1/MARCH/004.
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