Nasal drugdeliverysystem

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Nasal drugdeliverysystem

  1. 1. NASAL Welcome! DRUG DELIVERY SYSTEM Dr. Basavaraj K. Nanjwade M.Pharm., Ph.D Associate Professor [Company Name] Department of Pharmaceutics KLE University, Belgaum – 590010 Karnataka, INDIA03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 1
  2. 2. CONTENTS Novel Drug Delivery System Global trends in drug delivery systems Nasal Drug Delivery System Medical aspects Formulation Development Applications Conclusion03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 2
  3. 3. NOVEL DRUG DELIVERY SYSTEM - an overview03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 3
  4. 4. Novel drug delivery is one ofthe fastest growing healthcaresectors, with sales of drugsincorporating novel drugdelivery systems increasing @an annual rate of 15%03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 4
  5. 5. By 2010, the US drug delivery market alone will be worth $30 billion03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 5
  6. 6. There are great opportunities for companiesinvesting in R&D for new, improved drugdelivery system, allowing for improvedtherapeutic absorption and efficacy inpatients03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 6
  7. 7. Why Novel Drug Delivery system? To optimize drug’s therapeutic effect, convenience and dose To enhance a product’s life-cycle To improve `patient compliance To target drug delivery To control overall healthcare costs To facilitate biological drug delivery03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 7
  8. 8. The Novel Drug Delivery industry is comprised of companies seeking to develop ­ Novel alternatives to existing delivery systems Eg. implantable pumps ­ Enhancements to existing systems Eg. sustained release oral dosage forms to reduce dosing frequency ­ Commercially enabling delivery systems that provide viable alternatives for therapeutics that are not fully developed and marketed because there are limited practical means of administration Eg. polar organics and other poorly absorbed therapeutics03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 8
  9. 9. Novel drug delivery companies have existed since the late 1960s, when Alza and Elan pioneered the oral methods of enhanced drug delivery The introduction of hypodermic devices but especially metered dose inhalers & nasal sprays, promoted the concept and absolute need for specific drug delivery systems for specific diseases03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 9
  10. 10. Today there are between 300 & 350 companiesworldwide with an interest in drug delivery, operating in afierce environment where the number of drug launches using proven delivery technology is growing More novel technologies such as pulmonary delivery of insulin or needle-less human growth hormone injections are under development and are yet to be commercialized 03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 10
  11. 11. Drug Delivery Systems Inject- Trans- Vaginal/Oral Mucosal Topical Ocular able dermal Anal Needle Nasal Active Needle- Buccal Passive less Pulmo- nary 03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 11
  12. 12. Global drug delivery market by administration mode Nasal 2% Ocular 2%Injectable/ Oral 53%Implant 3%Transdermal 8% Inhalation 32% 03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 12
  13. 13. AS AL N ST EM SY RY EL IVE D R UG D03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 13
  14. 14. Inhalation/pulmonary drug delivery system includes ² Metered dose inhalers ² Dry powder inhalers ² Inhalation solutions & suspensions (for nebulizers) ² Inhalation nasal sprays03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 14
  15. 15. Historically, nasal drug delivery system has received interest since ancient timesTherapy through intranasal administration has been an accepted form of treatment in the Ayurvedic system of Indian medicine03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 15
  16. 16. Nasal Drug Delivery System & Opportunity Annual market growth Development time vis-a-vis new chemical entity Development cost vis-a-vis new chemical entity Merits Limitations03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 16
  17. 17. 30% 11% Annual growth of Annual growth of locally acting systemically acting products products03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 17
  18. 18. Drug development time 10 – 14 years New Chemical Entity 2 – 5 years Nasal Drug Delivery03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 18
  19. 19. Drug development cost $300-600 mio New Chemical Entity $50 mio Nasal Drug Delivery03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 19
  20. 20. 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 mode03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 20
  21. 21. Merits... Lower dose & hence lower side effects Useful for both local & systemic drug delivery For CNS drugs, better site for rapid onset of action Eg. Inhalation anesthesia, Morphine etc.03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 21
  22. 22. 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 bioavailability03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 22
  23. 23. U TE R O ts S AL sp ec N A la di ca e -m03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 23
  24. 24.  The respiratory tract, which includes the  nasal mucosa  hypopharynx  large airways &  small airways  provides a relatively large mucosal surface area of approx. 100 m2 (in normal adult) for drug absorption03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 24
  25. 25. Cross-sectional view Nasal site of drug spray & absorption Pathways for nasal absorption03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 25
  26. 26. Cross-sectional view a – nasal vestibule d – middle turbinate b – palate e – superior turbinate (olfactory mucosa) c – inferior turbinate f – nasopharynx03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 26
  27. 27. Site of drug spray & absorption03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 27
  28. 28. 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 fluid 03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 28
  29. 29. Transneuronal absorption Olfactory nerve – 1st cranial sensory nerve03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 29
  30. 30. Venous drainage03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 30
  31. 31. Nasal enzymes•Cytochrome P 450 dependent onooxygenases, Lactate dehydrogenase, Oxidoreductase, Hydrolases, Esterase,lactic dehydogenase, malic enzymes, lysosomalproteinases, steroid hydroxylases., etc.,•Cytochrome P450 dependent mono oxygenases hasbeen reported to catalyse the metabolism of xenobiotics,nasal decongestants, nocotine, cocaine, phenacetin,nitrosamine progesterone etc.,•Insulin zinc free was hydrolysed slowly by leusineaminopeptidase,•PG of E series was inactivated 15 hydroxyprostaglandindehydrogenase 03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 31
  32. 32. Nasal enzymes – contd.,•Progesterone and testosterone weremetabolized by several steroidhydroxylases in the nasal mucosa of rats 03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 32
  33. 33. 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 pH 03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 33
  34. 34. of ss te la u c ic l ro ut sa pe na ra or e f Th gs d ru03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 34
  35. 35. Therapeutic class of drugs 1. β2 adrenergic agonists 2. Corticosteroids 3. Antiviral 4. Antibiotics 5. Antifungal 6. More recently, vaccines03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 35
  36. 36. Drugs commonly administered through pulmonary route include1. Terbutaline Sulphate - β2 adrenergic agonist2. Salbutamol - β2 adrenergic agonist3. Budesonide - corticosteroid4. Ipratropium Bromide - anticholinergic5. Sodium Chromoglycate – mast cell stabilizer 03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 36
  37. 37. Formulation Development03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 37
  38. 38. Formulation Development Dosage form Factors affecting drug absorption Formulation considerations Physiological Pharmaceutical03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 38
  39. 39. Dosage forms Liquid drop Liquid spray/nebulizers Aerosol Suspension spray/nebulizers Gel Sustained release03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 39
  40. 40. Drug concentrationFactors 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 solubility 03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 40
  41. 41. Physiological effects- Drug metabolism in the respiratory tract & reduction of systemic effect- Protein binding- Mucociliary transport causing increased or decreased drug residence time 03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 41
  42. 42. Physiological effects....- Local toxic effects of the drug Eg., edema, cell injury, or altered tissue defenses- Local or systemic effects of propellants, preservatives, or carriers 03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 42
  43. 43. Pharmaceutical- Physico-chemical properties of a drug candidate- Methods to enhance drug absorption- Spray pump devices 03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 43
  44. 44. 1. Effect of particle size2. Effect of molecular size3. Effect of solution pH4. Effect of drug lipophilicity5. Effect of drug concentration 03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 44
  45. 45. 1. Effect of particle size (aerodynamic size distribution)- Access to distal airways is a function of particle size- Large particles (> 7 microns) will be lost in the gastrointestinal tract- Small particles (< 3 microns) will be lost in exhaled breathe- Intermediate particles (3 to 7 microns) reach the actual site of action 03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 45
  46. 46. 2. Effect of molecular size- Higher the molecular size, lower the nasal absorption- A good systemic bioavailability can be achieved for molecules with a molecular weight of up to 1000 Daltons when no absorption enhancer is used03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 46
  47. 47. 2. Effect of molecular size.....- With the assistance of absorption enhancer, a good bioavailability can be extended to a molecular weight of at least 6000 Daltons Absorption enhancers: Polyacrylic acid Sodium Glycocholate Sodium Deoxycholate Polysorbate 80 etc.03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 47
  48. 48. 3. Effect of solution pH- Nasal absorption is pH dependent- Absorption is higher at a pH lower than the dissociation constant (pKa) of the molecule- Absorption is lower as the pH increases beyond the dissociation constant03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 48
  49. 49. 4. Effect of drug lipophilicity- Polar (water soluble) drugs tend to remain on the tissues of the upper airway- Non-polar (lipid soluble) drugs are more likely to reach distal airways- Lipid soluble drugs are absorbed more rapidly than water soluble drugs03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 49
  50. 50. 5. Effect of drug concentration- Absorption depends on the initial concentration of the drug- The absorption follows first-order kinetics03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 50
  51. 51. Methods to enhance nasal absorption of drugs Structural modification Salt or ester formation Formulation design03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 51
  52. 52. SPRAY PUMP DEVICES - Unidose - Bidose - Multidose03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 52
  53. 53. Bidose Unidose03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 53
  54. 54. Multidose03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 54
  55. 55. LEADING PUMP SUPPLIERS Pfeiffer, Germany Valois, France Becton Dickinson, France Nemo, Spain03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 55
  56. 56. Applications Delivery of non-peptide pharmaceuticalsDelivery of peptide-based pharmaceuticals Delivery of diagnostic drugs03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 56
  57. 57. 1. Delivery of non-peptide pharmaceuticalsDrugs with extensive pre-systemic metabolism, such as- progesterone- estradiol- propranolol- nitroglycerin- sodium chromoglyatecan be rapidly absorbed through the nasal mucosawith a systemic bioavailability of approximately 100% 03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 57
  58. 58. 2. Delivery of peptide-based pharmaceuticalsPeptides & proteins have a generally low oralbioavailability because of their physico-chemicalinstability and susceptibility to hepato-gastrointestinal first-pass eliminationEg. Insulin, Calcitonin, Pituitary hormones etc.Nasal route is proving to be the best route for suchbiotechnological products03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 58
  59. 59. 3. Delivery of diagnostic drugs Diagnostic agents such as • Phenolsulfonphthalein – kidney function • Secretin – pancreatic disorders • Pentagastrin – secretory function of gastric acid 03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 59
  60. 60. IO N LU S O N C C03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 60
  61. 61. 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 drugs03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 61
  62. 62. 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 effects03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 62
  63. 63. Attractive for delicate molecules allowing systemic administration without significant degradation03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 63
  64. 64. Nasal drug delivery system offers flexibility for multiple formulations ranging from nasal drop to suspension spray03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 64
  65. 65. Recent activities indicate a bright prospect for site-specific delivery of biotechnological products such as Insulin & other hormones03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 65
  66. 66. Cell No: 00919742431000; E-mail: bknanjwade@yahoo.co.in03/10/2009 Sinhgad College of Pharmacy, Vadgaon, Pune-411041 66

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