Ndds 9 Nasal Drug Delivery System

NDDS TOPICS BY PROF. SHASHANK CHAURASIYA

1. NASAL DRUG DELIVERY SYSTEM 1 Prepared By: Prof. Shashank Chaurasiya Asst. Professor Bansal College of pharmacy, Bhopal

2. Novel drug delivery is one of the fastest growing healthcare sectors, with sales of drugs incorporating novel drug delivery systems increasing @ an annual rate of 15% 2 ABOUT

3. O r al Injec t - able Mucosal Trans- dermal Ocular Vaginal/ Anal Ne e d l e Ne e d l e- less Nasal Buccal Pulm o - nary Active Passive Topical DRUG DELIVERY STSTEM 3

4. GLOBAL DRUG DELIVERY MARKET BY ADMINISTRATION MODE Oral 53% Inhation 32% Transdermal 8% Ocular 2% I nj e c t a bl e / Impl ant 3% Nasal 2% 4

5. Nasal Drug Delivery New Chemical Entity $50 million $300-600 million DRUG DEVELOPMENT COST 5

6. New Chemical Entity Nasal drug Delivery 2 – 5 years 10 – 14 years DRUG DEVELOPMENT TIME 6

7. It is also a type of muco-adhesive drug delivery system. Intranasal Medication administration offers a truly “Needleless ” solution to drug delivery. Therapy through intranasal administration has been an accepted as form of treatment in the Ayurvedic system of Indian medicine INTRODUCTION 7

8. NASAL ENZYMES: Cytochrome p-450 dependent oxygenase , dehydrogenase , oxydoreductase , hydrolase s , esterase s, la c tic d e h ydroge na s e s , l a c ta t e acid m alic enzy m es, l y soso m al proteinases, st eroid hy d roxylases etc . NASAL PH: A dult nasal secretion pH: 5.5-6.5 Infants & children : 5-6.7. Lysosome in the nasal secretion helps as antibacterial & its activity is diminished in alkaline pH. 8

9. ADVANTAGES OF NASAL DRUG DELIVERY SYSTEM 1 A noninvasive route. Hepatic first – pass metabolism is absent. Rapid drug absorption. Quick onset of action. The bioavailability of larger drug molecules can be improved by means of absorption enhancer or other approach. Better nasal bioavailability for smaller drug molecules. Drugs which can not be absorbed orally may be delivered to the systemic circulation through nasal drug delivery system. Convenient route when compared with parenteral route for long term therapy. 9

10. LIMITATIO N S The absorption enhancers used to improve nasal drug delivery system may have histological toxicity which is not yet clearly established Absorption surface area is less when compared to GIT. Once the drug administered can not be removed . Nasal irritation. 10

11. ANATOMY OF NOSE 11

12. 12

13. Site of drug spray & absorption 13

14. NOSE BRAIN PATHWAY 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 brain. This area is termed the nose brain pathway and offers a rapid, direct route for drug delivery to the brain. Olf ac t ory mucosa Highly vascular nasal mucosa Bra i n CSF 14

15. 15 MECHANISM OF DRUG ABSORPTION Aq route of transport. Slow and passive. Transport through lipoidal membrane Active transport via carrier mediated means. Parac e llular transport T ranscellular transport

16. 17 FORMULATION DEVELOPMENT Dosage form Formulation considerations Factors affecting drug absorption Physiological Pharmaceutical

17. 18 DOSAGE FORMS Liquid drop Gel Sustained release Liquid spray/nebulizers Aerosol Suspension spray/nebulizers

18. 19 FACTORS AFFECTING DRUG ABSORPTION Drug concentration Mucosal contact time pH of the absorption site Size of the drug particle Relative lipid solubility Molecular weight of the drug

19. 20 PHYSIOCHEMICAL PROPERTIES OF DRUGS Effect of perfusion rate Effect of perfusate volume Effect of solution pH Effect of drug lipophilicity Effect of initial drug concentration. Chemical form Polymorphism Partition coefficient Solubility and dissolution Partical size

20. 21 PHYSIOLOGICAL FACTORS Blood flow Enzymatic degradation Volume of administration

21. METHODS TO ENHANCE NASAL ABSORPTION OF DRUGS Structural modification Formulation design Salt or ester formation 22

22. 23 Strategies for improving drug availability in nasal administration: Improve nasal residence time Apply drug anteriorly Formulation with polymers Use of biodegradable microspheres Enhance nasal absorption Increase the rate at which drug passes through nasal absorption.

23. 24 FORMULATION EXCIPIENTS Buffer capacity-citrate buffer Osmolarity-sodium acid phosphate Viscosifying agent-carbapol,cellulose Solublizer-labrasol,surfactants Preservatives-benzalkonium cl,parabens Antioxidants-tocopherols,sodium metabisulphide Humectants-glycerine,sorbitol

24. 25 APPLIC A TIONS Delivery of non-peptide pharmaceuticals Delivery of diagnostic drugs Delivery of peptide-based pharmaceuticals Cns delivery through nasal route Nasal vaccination

25. Drugs with extensive pre-systemic metabolism, such as progesterone estradiol propranolol nitroglycerin sodium chromoglyate can be rapidly absorbed through the nasal mucosa with a systemic bioavailability of approximately 100% 26 1 . Delivery of non-peptide pharmaceuticals:

26. Peptides & proteins - low oral bioavailability because of their physico-chemical instability and susceptibility to hepato gastrointestinal first-pass elimination 27 2.Delivery of peptide-based pharmaceuticals: for such Eg. Insulin, Calcitonin, Pituitary hormones etc. Nasal route i s p roving t o b e t h e b est route biotechnological products

27. Diagnostic agents such as Phenolsulfonphthalein – kidney function Secretin – pancreatic disorders Pentagastrin – secretory function of gastric acid 28 3 . Delivery of diagnostic drugs

28. 4.CNS delivery through nasal route : The delivery of drugs to the CNS from the nasal route may occur via olfactory neuroepithelium Drug delivery through nasal route into CNS has been reported for Alzheimer’s disease brain tumours epilepsy iv. pain and sleep disorders. 29

29. 5.Systemic delivery: Fast and extended drug absorption Ex.- analgesics (morphine), cardiovascular drugs(propranolol) hormones (levonorgestrel, progesterone) antiviral drugs Marketed formulation- zolmitriptan and sumatriptan 30

30. Nasal mucosa is the first site of contact with inhaled antigens and therefore, its use for vaccination, especially against respiratory infections, has been extensively evaluated. Ex. Human efficacy of intranasal vaccines include those against influenza A and B virus, proteosoma ‐ influenza, adenovirus ‐ vectored influenza, group B meningococcal native, attenuated respiratory syncytial virus and parainfluenza 3 virus. 6.Nasal vaccines 31

31. SPRAY PUMP DEVICES - Unidose Bidose Multidose 32

32. DOSAGE FORMS Liquid drop Liquid spray/nebulizers Aerosol Suspension spray/nebulizers Gel Sustained release 33

33. Nasal drops Most simple and convenient systems developed for nasal delivery. It has been reported that nasal drops deposit human serum albumin in the nostrils more efficiently than nasal sprays. Disadvantage-lack of the dose precision . 34

34. Lincoln Pharma wins patent for a novel nasal drug delivery system Presently in India anti-vomiting treatments are available in the conventional form of tablet and injection which take longer time to bring relief. LPL becomes the first company in India to introduce an anti-vomiting treatment in the form of a Nasal spray pump. 40

35. Nasal Gels 41 Nasal g els a r e hig h - vi s c os i ty thi c k en e d so l ution s or suspensions. Advantages of a nasal gel Reduction of post-nasal drip due to high viscosity, Reduction of taste impact due to reduced swallowing, Reduction of anterior leakage of the formulation, R educti o n o f irri t a t ion b y usin g so o thin g / e m ollie n t excipients and target to mucosa for better absorption.

36. Mucosal Atomization Device (MAD) Device designed to allow emergency personnel to delivery nasal medications as an atomized spray. Broad 30-micron spray ensure excellent mucosal coverage. 42

37. Nasal vaccines Nasal mucosa is first site of contact with inhaled antigens and, therefore, its use for vaccination, especially against respiratory infections Promising alternative to the classic parenteral route, because it is able to enhance the systemic levels of specific immunoglobulin G and nasal secretary immunoglobulin A. Examples of human efficacy of intranasal vaccines include those against influenza A and B virus, proteosoma influenza e 40 Intra nasal H1N1 vaccine Nasovac by Serum Institut

38. Therapeutic class of drugs for nasal route 41 2 1. adrenergic agonists Corticosteroids Antiviral Antibiotics Antifungal More recently, vaccines

39. CON T … An accessible alternative route for drug administration. Provides future potential for several drugs through the development of safe and efficacious formulations for simple, painless and long ‐ term therapy. Drugs can be directly target to the brain in order to attain a good therapeutic effect in CNS with reduced systemic side effects. Much has been investigated and much more are to be investigated for the recent advancement of nasal drug delivery system. 46

40. . THANK YOU… THANK YOU…