2. What is “NASAL” Drug Delivery system?

13. 1. The anterior one-third of the nasal cavity viewed in cross-section reveals a central septum dividing the two cavities. This region, including the proximal portion of the inferior and middle turbinates, is nonciliated . 2. In the posterior two-thirds of the nasal cavity, clearance of deposited particles occurs by slow spreading of the mucus layer into the ciliated regions along the inferior and middle meatuses, followed by a more rapid mucociliary clearance into the nasopharynx from where they are swallowed. 3. Approximately 1 L of mucus is transported from the anterior part to the posterior part of the nose per day. It takes approximately 20–30 min for the whole mucus layer to be renewed. a – nasal vestibule d – middle turbinate b – palate e – superior turbinate (olfactory mucosa) c – inferior turbinate f – nasopharynx

14. Site of drug spray & absorption

16. POSSIBLE DRUG ABSORPTION PATHWAYS

19.  Absorption through the supporting cells & the surrounding capillary bed - venous drainage

22. Formulation Development

23. Formulation Development Dosage form Formulation considerations Factors affecting drug absorption Physiological Pharmaceutical

24. Dosage forms Liquid drop Liquid spray/nebulizers Suspension spray/nebulizers Gel Sustained release Aerosol

25. Factors affecting drug absorption Drug concentration Vehicle of drug delivery Mucosal contact time pH of the absorption site Size of the drug molecule Relative lipid solubility Degree of drug’s ionization

27. Physiological effects - Drug metabolism in the respiratory tract & reduction of systemic effect - Mucociliary transport causing increased or decreased drug residence time - Protein binding - Local or systemic effects of propellants, preservatives, or carriers - Local toxic effects of the drug Ex., edema, cell injury, or altered tissue defenses

28. 1. Effect of particle size 2. Effect of molecular size 3. Effect of solution pH 5. Effect of drug concentration 4. Effect of drug lipophilicity

30. 3. Effect of solution pH - Nasal absorption is pH dependent - Absorption is lower as the pH increases beyond the dissociation constant - Absorption is higher at a pH lower than the dissociation constant (pKa) of the molecule 4. Effect of drug lipophilicity - Polar (water soluble) drugs tend to remain on the tissues of the upper airway - Lipid soluble drugs are absorbed more rapidly than water soluble drugs - Non-polar (lipid soluble) drugs are more likely to reach distal airways 5. Effect of drug concentration - The absorption follows first-order kinetics - Absorption depends on the initial concentration of the drug

41. Applications Delivery of non-peptide pharmaceuticals Delivery of diagnostic drugs Delivery of peptide-based pharmaceuticals

43. 2. Delivery of peptide-based pharmaceuticals Peptides & proteins have a generally low oral bioavailability because of their physico-chemical instability and susceptibility to hepato-gastrointestinal first-pass elimination Eg. Insulin, Calcitonin, Pituitary hormones etc. Nasal route is proving to be the best route for such biotechnological products

44. Basic concepts for achieving improved nasal peptide and protein delivery.

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

48. REFERENCES: 1. Encyclopedia of pharmaceutical technology. 3 rd Edition . Vol 1. Page :1201 by JAMES SWARBRICK. 2. Text book of Novel Drug Delivery System by Chien, 2 nd Edition. 3. Shaji J and Marathe S.W. NASAL DRUG DELIVERY SYSTEM: OPPORTUNITIES & CHALLENGES INDIAN DRUGS Vol. 45 No. 5 May 2008 Pg no (345 – 353)