Nasal Drug Delivery System

Presentation on Nasal Drug Delivery System...

1. nasal drug delivery system SARDAR BHAGWAN SINGH P.G. INSTITUTE OF BIO MEDICAL SCIENCES AND RESEARCH, BALAWALA, DEHRADUN, UTTARAKHAND PRESENTED BY- GUIDED BY- NAMAN PANT Mrs. GAUREE KUKRETI M.Pharm. (Pharmaceutics) Assistant professor SECOND SEMINAR (MPHR 120) 2016-17 1

2. ORGANIGATION- Introduction Anatomy & Physiology Of Nasal cavity Mechanism of drug absorption Advantages & Disadvantages Factors affecting drug absorption Components of nasal drug formulations Various drug delivery formulations Applications of nasal drug delivery systems Some marketed products Conclusion 2

3. What is Nasal Drug Delivery System ? 3

4. Introduction- Administration of drug through nasal route is referred as Nasal drug delivery system. Nasal route is an alternative to invasive administrations and provides a direct access to the systemic circulation. The nose offers easy access to a large mucosal surface well suited for drug delivery. About 2% of the overall drug delivery is administered via the nasal route. In recent years many drugs have been shown to achieve better systemic bioavailability through nasal route than by oral administration. 4 (1) Singh AK, Singh A, Madhav NV, Nasal Cavity: A Promising Transmucosal Plateform for Drug Delivery & Research, Journal of Drug Delivery & Therapeutics, 2012, 2(3), Pp- 22-23

5. Anatomy and physiology of nasal cavity- 5 (2) Kaur H, Singh C, Gupta GD, Nasal Drug Delivery: Review, Indo Anerican Journal of Pharmaceutical Research, 5(8), 2015, Pp. 2522-2530

6. The nasal cavity is run from the nasal vestibule to the nasopharynx which has depth of approximately 12-14cm. The nasal vestibule, the respiratory region and the olfactory region are the three main regions of the nasal cavity. The sub mucosal zone of the nasal mucosa directly connects to the systemic circulation, thus avoids first pass metabolism. Nasal cavity is about 60mm in length. The nasal cavity is covered with a mucous membrane which can be divided into nonolfactory and olfactory epithelium areas. The nonolfactory area includes the nasal vestibule and respiratory region. Nasal blood flow external & internal carotid arteries. Nasal secretions :- Nasal secretions are secreted by goblet cells, nasal glands and transudate from plasma. Composition :- 95% water, 1-2% salt, 2-3% mucin. in trace amount Na, K, Ca, Albumin also present. Nasal enzymes :- Monooxygenase, lactate dehydrogenase, oxidoreductase, phosphates , hydrolases, esterase's, etc. Nasal pH :- 5.5-6.5 (adults) 5.0-6.7 (infants & child) 6

7. Functions of nose- Smell Detection 7 (3) Mygind N, Dahl R, Anatomy, Physiology & Function of the Nasal Cavities in Health & Disease, Advance Drug Delivery Reviews, (29), 1998, Pp. 3-12

8. Mechanism of drug absorption- By paracellular process By transcellular process 8

9. It involves an aqueous route of transport. It refers to the transfer of drug by passing through the intracellular spaces between the cells. The molecular weight greater then 1000 Daltons having drugs shows poor bioavailability. It involves transport through a lipoidal route. It responsible for the transport of lipophilic drugs that show a rate dependency on their lipophilicity. Drugs cross the cell membrane by an active transport route or transport through the opening of tight junctions. Paracellular process Transcellular process 9 (4) Laksitorini M, Vivitri D, Paul KK, Pathways and Progress in Improving Drug Delivery Through the Intestinal Mucosa & Blood Brain Barriers, AuthorManuscript,2014,5(10),Pp.1143-1163

10. Pathway of drug absorption- 10 (5) Wen MM, Olfactory Targeting Through Intranasal Delivery of Biopharmaceutical Drugs to Brain, Discovery Medicine, (6) ,2011.

11. Nose brain pathway- 11 Olfactory mucosa Nerves Brain CSF Highly vascular nasal mucosa The olfactory mucosa (smelling area in nose) is in direct contact with the brain and CSF. Medications absorbed across the olfactory mucosa directly enter the CSF. This area is termed the nose brain pathway and offers a rapid, direct route for drug delivery to the brain (6) Chen XQ, Fawcett JR, Delivery of Nerve Growth Factor to Brain via the Olfactory Pathway, Journal of Alzheimer's Disease, (1), 1998, Pp.35-44

12. 12 ADVANTAGES- Drug degradation that is observed in the gastrointestinal tract is absent. Hepatic first pass metabolism is avoided. Rapid drug absorption and quick onset of action can be achieved. The bioavailability of larger drug molecules can be improved by means of absorption enhancer or other approach. The nasal bioavailability for smaller drug molecules is good. Drugs that are orally not absorbed can be delivered to the systemic circulation by nasal drug delivery. Nasal route is an alternate to parental route, especially, for protein and peptide drugs. Convenient for the patients, especially for those on long term therapy, when compared with parental medication.

13. Disadvantages- The histological toxicity of absorption enhancers used in nasal drug delivery system is not yet clearly established. Relatively inconvenient to patients when compared to oral delivery systems since there is a possibility of nasal irritation. Nasal cavity provides smaller absorption surface area when compared to GIT. There is a risk of local side effects and irreversible damage of the cilia on the nasal mucosa, both from the substance and from constituents added to the dosage form. Certain surfactants used as chemical enhancers may disrupt and even dissolve the membrane in high concentration. 13 (7) Vyas SP, Khar RK, Controlled Drug Delivery, Vallabh Prakashan , ed (2),2012, Pp. 301-325

14. Factors affecting absorption of drug- Chemical form: The form of a drug can be important in determining absorption. Example : Nasal absorption of carboxylic acid esters of L-Tyrosine significantly greater than that of L-Tyrosine. Polymorphism: Polymorphism is known to affect the  dissolution rate , solubility of drug and thus their absorption through biological membranes. Molecular Weight: A linear correlation has been reported between the absorption of drugs and molecular weight up to 300 Daltons. Absorptions decreases significantly if the molecular weight is greater than 1000 Daltons (except with the use of absorption enhancers). Particle Size: It has been reported that particle sizes 10 -20 μm are deposited in the nasal cavity. Particles Which are less than 2 μm can be retained in the lungs, and particles of greater than 20 μm size exhaled with air. 14 (8) Jadhav KR, Manoj N, Shaikh IM, Nasal Drug Delivery- Factors Affecting & applications, Current Drug Therapy, (2), 2007, Pp.27-38

15. Enhancement of drug absorption- 15 Surfactants Bile salts Chelaters Fatty acids Phospholipids Methyl cellulose, CMC, Polyacrylic acid Starch, Albumin, Gelatin, Dextrin Histamine, Prostaglandin E1, Terbutaline (9) Merkus FWHM, Schiffer NGM, Hermens WAJJ, Absorption Enhancers in Nasal Drug Delivery : Efficacy &Safety, Journal of Controlled Release, 24,1993, Pp. 201-208

16. Components of nasal formulations- 16 (10) Turker S, Onur E, Ozer Y, Nasal Route & Drug Delivery System, Pharma World Science, (26), 2004, Pp. 137-142

17. Various nasal drug delivery formulations- 17 (11) Djupesand GP, Nasal Drug Delivery devices: Characteristics & Performance in a Clinical Perspective, Drug Delivery and Transl. Research, 2013, (3), Pp. 42-62

18. Nasal sprays- Larger surface area of coverage. Smaller liquid particle size allowing thin layer to cover mucosa. Less run-off out the nasal cavity. Types of spray pump devices- Multidose & Unidose. 18 (12) Bommer R, Kern J, Hennes K, Nasal Drug Delivery System, Medical Device Technology, (10), 2004, Pp. 2-5

19. Site of drug spray & absorption- Site of drug spray Site of drug absorption 19

20. Nasal Drops- Nasal drop devices are the most traditional dispensing systems. Nasal drops may be suitable for infants. In adults, drops into the nasal cavity mostly lead to a rapid clearance of the drug from nasal cavity towards to the throat. 20 (13) Kaur H, Singh C, Gupta GD, Nasal Drug Delivery: Review, Indo Anerican Journal of Pharmaceutical Research, 5(8), 2015, Pp. 2522-2530

21. Metered dose pump- Metered dose sprays include the container, the pump with the valve and the actuator. The dose accuracy of metered dose pump spray is depends upon the surface tension and viscosity of the formulation. Propane, n-butane, isobutane, Dimethyl ether (DME) and methyl ethyl ether are some examples of propellant. 21

22. Saturated cotton pledgets- Cotton pledgets are soaked in the drug and placed in the nasal cavity . Commonly used for local anesthetic’s vasoconstrictors etc . 22

23. Nasal gels- Nasal gels are high viscosity thickened solution or suspensions. ADVANTAGES- Reduction of post-nasal drip due to high viscosity Reduction of taste impact due to reduce swelling. Reduction of irritation by using soothing/emollient excipients and target to mucosa for better absorption. 23 (14) Rathnam G, Narayanan, Carbopol Based Gels for Nasal Delivery of Progestrone , AAPS Pharmaceutical Science Technology, 9(4), 2008, Pp- 1078-1082

24. Nasal ointment- These are translucent, homogenous, viscous, semisolid preparation intended to be instilled in the nose. Due to their viscosity they will not ooze out of the nose. 24 (15) http://retailpharmaindia.com/product/bactroban-ointment-5-gm accessed on 19/04/2017

25. Mucosal Atomization Device (MAD)- This device designed to allow emergency personal to delivery nasal medications as an atomized spray. Broad 30 micron spray ensure excellent mucosal coverage. It is disposable and single use only. 25

26. Nebulizer- Nebulizer is a drug delivery device used to administer medication in the form of a mist inhaled into the lungs. The most commonly used nebulizers are Jet nebulizers , which are also called "atomizers". Jet nebulizers are commonly used for patients in hospitals who have difficulty using inhalers . The main advantage of the Jet nebulizer is related to its low operational cost. 26 (16) Dahl R, Anatomy, Physiology & Function of the Nasal Cavities in Health & Disease, Advance Drug Delivery Reviews, 29, 1998, Pp. 3-12

27. Nasal powder- This dosage form may be developed if solution and suspension dosage forms cannot be developed due to lack of drug stability. The advantages to the nasal powder dosage form are the superior stability of the formulation. Local application of drug is another advantage of this system. 27 (17) http://www.onzetrahcp.com accessed on 18/04/2017

28. Applications of nasal drug delivery system- Delivery of non-peptide pharmaceuticals Eg. Progesterone, estradiol, propranolol, nitroglycerin, sodium chromoglyate, etc. Delivery of peptide based pharmaceuticals Eg. Insulin, Calcitonin, Pituitary hormones etc. Delivery of Diagnostic Drugs Phenol sulfo naphthalene- For diagnosis of kidney functions Secretin- For diagnosis of pancreatic disorders Pentagastrin- For diagnosis of secretory functions of gastric acid. Cerulin- For diagnosis of Gallbladder function Vital dyes- Trypan blue and Evans blue (it can not enter in cranium because they can not pass through sheath) Delivery of drugs to Brain: For Treatment of Parkinson’s disease, Alzheimer disease. For Delivery of Melanocyte stimulating hormone, ACTH, Insulin to brain 28 (18) Ozer YA, Alternative Applications for Drug Delivery: Nasal & Pulmonary Routes, Nanometrials & Nanosystems for Biomedical applications, Springer,2007, Pp. 99-112

29. Evaluation of nasal drug delivery- In the case of nasal powders- Particle size, melting point, angle of repose, Carr's comprexibility index etc. In the case of nasal gels- Mucoadhessive strength, Flow property etc. In the case of nasal sprays- Clearity of liquid, sterilization, content drug delivery etc. In the case of nasal drops- Clearity test, sterilization, closure system etc. 29 In-vitro studies-

30. In-vivo studies- Various animal compartment models are used for in-vivo evaluation studies. The most convenient model is the anesthisized rat model. For most non-peptide drugs the results obtained in rats can accurately reflect the absorption profiles in humans. Some other animal models are- 30 Rabbit model Dog model Monkey model etc. (19) Selcan T, Onur E, Ozer Y, Nasal route & Drug Delivery System, Pharm. World Science, 2004, (26), Pp- 137-142

31. Some marketed products- 31

32. Some marketed products in india- 32 (20)http://www.zuventus.co.in/doctor_wise_products_selected.aspx?Medi_Id=146 accessed on 17/04/2017

33. Conclusion - NASAL DRUG DELIVERY OFFERS SUCH BENEFITS AS, -Rapid onset of action with lower dose & minimal side effects. -Has an advantages of site specific delivery with improved therapeutic effect -Attractive for delicate molecule allowing systemic circulation without significant degradation. Nasal drug delivery offers flexibility for multiple formulation ranging from nasal drop to nasal spray. Recent activities indicate a bright prospect for site specific delivery of biotechnological product such as insulin & other hormones. 33

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