Nasal Drug Delivery System

Nasal Drug Delivery is Part of the Novel Drug Delivery System(NDDS) for effective drug delivery to the Brain, Lungs, and Local administartion. It has its own challenges and advantages.

1. NASAL DRUG DELIVERY SYSTEM (PHARAMACEUTICAL TECHNOLOGY) PRESENTED BY : DARSHIL SHAH M.PHARM I st YEAR ROLL NO. 15 GUIDED BY : MS. HEMAL TANDEL The Maharaja Sayajirao University of Baroda 1

2. INTRODUCTION Administration of drug through nasal route is referred as nasal drug delivery system. Nasal drug delivery – which has been practiced for thousands of years, in the Ayurvedic systems of Indian medicine, it is also called “ NASAYA KARMA ”. It has been used for local effects extensively in decongestant and local activity. Nowadays, intranasal drug delivery is being considered as preferred route of drug delivery for systemic bioavailability. 2

3. ANATOMY OF NASAL CAVITY The nose is divided into two nasal cavities via the septum. There are three different functional regions a)Nasal vestibule b)Olfactory region c)Respiratory region The vestibular region : It is located at the opening of nasal passages and is responsible for filtering out the air borne particles. It is considered to be the least important of the three regions with regard to drug absorption. The olfactory region : olfactory mucosa (smelling area in nose) is in direct contact with the brain and CSF. 3

4. Medication absorbs across the olfactory mucosa directly enter the brain. The area is termed nose-brain pathway and offers a rapid , direct route for drug delivery to the brain. The respiratory region : The respiratory region is the largest having the highest degree of vascularity and is mainly responsible for systemic drug absorption. Nasal cavity is covered with mucous membrane Which contains goblet cells and secrets mucous. The mucus layer is cleared from the nasal cavity by cilia, and is renewed every 10 to 15 minutes. The mucus moves through the nose at an approximate rate of 5 to 6 mm/min resulting in particle clearance within the nose every 15 to 20 minutes. Various enzymes like Cytochrome P450, Glutathione S-transferase, Oxidoreductase, Hydrolyse, Esterase etc… The pH of the mucosal secretions ranges from 5.5 to 6.5 in adults and 5.0 to 6.7 in children. 4

5. ADVANTAGES : 1) Drug degradation that is observed in the GIT is absent. 2) Hepatic first pass metabolism is avoided. 3) Rapid drug absorption and quick onset of action can be achieved. 4) The bioavailability of larger drug molecules can be improved by means of absorption enhancer or other approach. 5) The nasal bioavailability for smaller drug molecules is good. 6) Drugs that are orally not absorbed can be delivered to the systemic circulation by nasal drug delivery. 7) Studies so far carried out indicate that the nasal route is an alternate to parenteral route, especially, for protein and peptide drugs. 8) Convenient for the patients, especially for those on long term therapy, when compared with parenteral medication. 9) Drugs possessing poor stability in GIT. fluids are given by nasal route. 10) Polar compounds exhibiting poor oral absorption may be particularly suited for this route of deli-very. 5

6. LIMITATIONS : 1) The histological toxicity of absorption enhancers used in nasal drug delivery system is not yet clearly established. 2) Relatively inconvenient to patients when compared to oral delivery systems since there is a possibility of nasal irritation. 3) Nasal cavity provides smaller absorption surface area when compared to GIT. 4) 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. 5) Certain surfactants used as chemical enhancers may disrupt and even dissolve membrane in high concentration. 6) There could be a mechanical loss of the dosage form into the other parts of the respiratory tract like lungs because of the improper technique of administration. 6

7. MECHANISM OF DRUG ABSORPTION 7

8. PATHWAY OF DRUG ABSORPTION 8

9. FACTORS AFFECTING DRUG ABSORPTION 1) Physiochemical properties of drug. Molecular size. Lipophilic-hydrophilic balance. Enzymatic degradation in nasal cavity. 2) Nasal Effect Membrane permeability. Environmental pH Mucociliary clearance Cold, rhinitis. 3) Delivery Effect Formulation (Concentration, pH, osmolarity) Delivery effects Drugs distribution and deposition. Viscosity 9

10. ENHANCEMENT OF DRUG ABSORPTION 10

11. FORMULATION VISCOSIFYING AGENTS DRUGS SOLUBILIZERS / SURFACTANT OSMOTIC AGENTS HUMECTANTS ANTIOXIDENTS PRESERVATIVES 11

12. VARIOUS DOSAGE FORMS NASAL DROPS Most simple and convenient system developed for delivery. Nasal drops delivered the drug to a larger area back in nasal cavity. The main disadvantage of this system is the lack of dose precision. 12

13. NASAL SPRAY Both suspension and solution can be formulated into nasal sprays Deliver an exact dose from 25 to 200 micrometer 13

14. NASAL GELS Nasal gels are high-viscosity thickened solution or suspension Advantages: Reduction of post-nasal drip due to high viscosity. Reduction of taste impact due to reduced swallowing. Reduction in leakage of formulation. Reduction of irritation by using emollient. 14

15. NASAL POWDERS Nasal powders are prepared if nasal solution and suspension dosage form can not be developed, such as lack of drug stability. Advantages: Absence of preservative Local application of drug Stability of formulation 15

16. METERED DOSE PUMPS Metered dose pumps include the container, the pump, with the valve and actuator. The dose accuracy of metered dose pumps depends upon surface tension and viscosity of the formulation. Propane, isobutane, dimethylether (DME), and methyl ethyl ether are some examples of propellant. 16

17. MUCOSAL ATOMIZATION DEVICE (MAD) The device is designed to allow emergency personnel to delivery nasal medication as atomized spray. Broad 30micron spray ensures excellent mucosal coverage. It is disposable and single use only. 17

18. EVALUATION OF NASAL DRUG DELIVERY In-vitro studies In the case of nasal powders- Particle size, melting point, angel of repose, carr’s index, etc In the case of nasal gels- Mucoadhessive strength, flow property etc. In the case of nasal spray- clarity of liquid, sterilization, content drug delivery etc. In the case of nasal drops- clarity test, sterilization, closure system etc. 18

19. EVALUATION OF NASAL DRUG DELIVERY In-vivo studies Various animal compartment models are used for in-vivo evaluation studies. The most convenient model is the anestheisized rat model. For most non-peptide drugs the results obtained in rats can accurately reflect the absorption profiles in human.\ Some other animal models are, Rabbit model Dog model Monkey model etc. 19

20. APPLICATIONS Delivery of non-peptide pharmaceuticals e.g. progesterone, testosterone, hydralazine etc. Delivery of peptide-based pharmaceuticals e.g. insulin, calcitonin, pituitary hormones etc. Delivery of Drugs to Brain through Nasal Cavity For treatment of Par-kinson’s disease, Alzheimer’s disease. For delivery of MSH, ACTH, Insulin to brain. 20

21. APPLICATIONS Delivery of Vaccines through Nasal Route The common diseases like measles, pertussis, meningitis and influenza causing pathogens are mainly enter into the body through the nasal mucosal surfaces and hence good candidates for nasal vaccines. Nasal delivery of vaccine produces both local as well as systemic immune responses Delivery of diagnostic drugs Phenolsulfonphthalein for diagnosis of the kidney Cerulin for diagnosis of gallbladder function Secretin for diagnosis of Pancreatic disorders Pentagastrin for diagnosis of secretory function of gastric acid 21

22. MARKETED FORMULATIONS 22

23. SOME MARKETED PRODUCTS IN INDIA 23

24. REFERENCE Article in International Journal of Research in Pharmaceutical Sciences · January 2010 https://www.researchgate.net/publication/49601002 Drug Delivery System : A Review (Book) Nasal administration Wikipedia https://en.wikipedia.org https://scholar.google.com/ 24

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