Nasal drug delivery

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Nasal drug delivery

  1. 1. NASAL DRUG DELIVERY SYSTEM
  2. 2. Inhalation/pulmonary drug delivery system includes Metered dose inhalers Dry powder inhalers Inhalation solutions & suspensions (for nebulizers) Inhalation nasal sprays2 3/23/2011
  3. 3. Historically, nasal drug delivery system has received interest since ancient times Therapy through intranasal administration has been an accepted form of treatment in the Ayurvedic system of Indian medicine.3 3/23/2011
  4. 4. Merits Avoidance of hepatic first-pass metabolism. Rate of absorption comparable to IV medication. Rapid onset of pharmacological action. User-friendly, painless, non-invasive, needle- free administration mode.4 3/23/2011
  5. 5. Merits...  Lower dose & hence lower side effects  Useful for both local & systemic drug delivery  For CNS drugs, better site for rapid onset of action E.g.. Inhalation anesthesia, Morphine etc.5 3/23/2011
  6. 6. Limitations Once administered, rapid removal of the therapeutic agent from the site of absorption is difficult Pathologic conditions such as cold or allergies may alter significantly the nasal bioavailability6 3/23/2011
  7. 7. NASAL ROUTE - medical aspects7 3/23/2011
  8. 8.  The respiratory tract, which includes the  nasal mucosa  hypo pharynx  large airways &  small airways  provides a relatively large mucosal surface area of approx. 100 m2 (in normal adult) for drug absorption8 3/23/2011
  9. 9. Cross-sectional view Nasal site of drug spray & absorption Pathways for nasal absorption9 3/23/2011
  10. 10. Cross-sectional view a – nasal vestibule d – middle turbinate b – palate e – superior turbinate (olfactory mucosa) c – inferior turbinate f – nasopharynx10 3/23/2011
  11. 11. Site of drug spray & absorption11 3/23/2011
  12. 12. Pathways for nasal absorption  Absorption through the olfactory neurons - transneuronal absorption. Olfactory epithelium is considered as a portal for substances to enter CNS  Absorption through the supporting cells & the surrounding capillary bed - venous drainage  Absorption into the cerebrospinal fluid12 3/23/2011
  13. 13. Transneuronal absorption Olfactory nerve – 1st cranial sensory nerve13 3/23/2011
  14. 14. Nasal enzymes • Cytochrome P 450 dependent onooxygenases, Lactate dehydrogenase, Oxidoreductase, Hydrolases, Esterase, lactic dehydogenase, malic enzymes, lysosomal proteinases, steroid hydroxylases., etc. • Cytochrome P450 dependent mono oxygenases has been reported to catalyse the metabolism of xenobiotics, nasal decongestants, nocotine, cocaine, phenacetin, nitrosamine progesterone etc. • Insulin zinc free was hydrolysed slowly by leusine aminopeptidase, • PG of E series was inactivated 15 hydroxyprostaglandin dehydrogenase14 3/23/2011
  15. 15. Nasal enzymes – contd., Progesterone and testosterone were metabolized by several steroid hydroxylases in the nasal mucosa of rats.15 3/23/2011
  16. 16. Nasal pH • Nasal secretion of adult : 5.5-6.5 • Infants and children: 5-6.7 • It becomes alkaline in conditions such as acute rhinitis, acute sinusitis. • Lysozyme in the nasal secretion helps as antibacterial and its activity is diminished in alkaline pH16 3/23/2011
  17. 17. Therapeutic class of drugs for nasal route17 3/23/2011
  18. 18. Therapeutic class of drugs 1. β2 adrenergic agonists 2. Corticosteroids 3. Antiviral 4. Antibiotics 5. Antifungal 6. More recently, vaccines18 3/23/2011
  19. 19. Drugs commonly administered through pulmonary route include 1. Terbutaline Sulphate - β2 adrenergic agonist 2. Salbutamol - β2 adrenergic agonist 3. Budesonide - corticosteroid 4. Ipratropium Bromide - anticholinergic 5. Sodium Chromoglycate – mast cell stabilizer19 3/23/2011
  20. 20. Formulation Development20 3/23/2011
  21. 21. Formulation Development Dosage form Dosage form Factors affecting drug absorption Factors affecting drug absorption Formulation considerations Formulation considerations Physiological Pharmaceutical21 3/23/2011
  22. 22. Dosage forms Liquid drop Liquid spray/nebulizers Aerosol Suspension spray/nebulizers Gel Sustained release22 3/23/2011
  23. 23. Drug concentration Factors affecting Vehicle of drug delivery drug absorption Mucosal contact time Degree of drug’s ionization pH of the absorption site Size of the drug molecule Relative lipid solubility23 3/23/2011
  24. 24. Physiological effects - Drug metabolism in the respiratory tract & reduction of systemic effect - Protein binding - Mucociliary transport causing increased or decreased drug residence time24 3/23/2011
  25. 25. Physiological effects.... - Local toxic effects of the drug E.g., edema, cell injury, or altered tissue defenses - Local or systemic effects of propellants, preservatives, or carriers25 3/23/2011
  26. 26. Pharmaceutical effects - Physico-chemical properties of a drug candidate - Spray pump devices - Methods to enhance drug absorption26 3/23/2011
  27. 27. 1. Effect of particle size 2. Effect of molecular size 3. Effect of solution pH 4. Effect of drug lipophilicity 5. Effect of drug concentration27 3/23/2011
  28. 28. Methods to enhance nasal absorption of drugs  Structural modification  Salt or ester formation  Formulation design28 3/23/2011
  29. 29. SPRAY PUMP DEVICES Unidose Bidose Multidose29 3/23/2011
  30. 30. Applications Delivery of non-peptide pharmaceuticals Delivery of peptide-based pharmaceuticals Delivery of diagnostic drugs30 3/23/2011
  31. 31. Delivery of non-peptide pharmaceuticals  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%31 3/23/2011
  32. 32. 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 E.g. Insulin, Calcitonin, Pituitary hormones etc.  Nasal route is proving to be the best route for such biotechnological products32 3/23/2011
  33. 33. Delivery of diagnostic drugs Diagnostic agents such as • Phenolsulfonphthalein – kidney function • Secretin – pancreatic disorders • Pentagastrin – secretory function of gastric acid33 3/23/2011
  34. 34. CONCLUSION  Nasal route is a part of drug delivery strategy that is emerging to be a fastest growing drug delivery system with an annual growth of  11% for locally acting drugs  &  30% for systemically acting drugs34 3/23/2011
  35. 35.  Nasal drug delivery offers such benefits as  Rapid onset of action with lower dose & minimal side effects  Has an advantage of site-specific delivery with improved therapeutic effects35 3/23/2011
  36. 36. Attractive for delicate molecules allowing systemic administration without significant degradation Nasal drug delivery system offers flexibility for multiple formulations ranging from nasal drop to suspension spray36 3/23/2011
  37. 37. Recent activities indicate a bright prospect for site-specific delivery of biotechnological products such as Insulin & other hormones37 3/23/2011
  38. 38. THANK YOU38 3/23/2011

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