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    Nasal Drug Delivery System

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    warezisgr8
    The document discusses nasal drug delivery systems. Key points include: - Nasal delivery provides a non-invasive alternative to injections with rapid drug absorption and onset of effects. It avoids hepatic first-pass metabolism. - The nasal cavity offers a large mucosal surface area for drug absorption. Drugs are absorbed both locally and systemically via the olfactory neurons, blood vessels, or cerebrospinal fluid. - Nasal delivery is well-suited for peptides and other drugs susceptible to degradation, with bioavailability comparable to IV injection and lower side effects than oral administration.

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    Nasal Drug Delivery System

    Uploaded by

    warezisgr8
    217 views66 pages
    The document discusses nasal drug delivery systems. Key points include: - Nasal delivery provides a non-invasive alternative to injections with rapid drug absorption and onset of effects. It avoids hepatic first-pass metabolism. - The nasal cavity offers a large mucosal surface area for drug absorption. Drugs are absorbed both locally and systemically via the olfactory neurons, blood vessels, or cerebrospinal fluid. - Nasal delivery is well-suited for peptides and other drugs susceptible to degradation, with bioavailability comparable to IV injection and lower side effects than oral administration.

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    Nasal Drug Delivery System

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    The document discusses nasal drug delivery systems. Key points include: - Nasal delivery provides a non-invasive alternative to injections with rapid drug absorption and onset of effects. It avoids hepatic first-pass metabolism. - The nasal cavity offers a large mucosal surface area for drug absorption. Drugs are absorbed both locally and systemically via the olfactory neurons, blood vessels, or cerebrospinal fluid. - Nasal delivery is well-suited for peptides and other drugs susceptible to degradation, with bioavailability comparable to IV injection and lower side effects than oral administration.

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    217 views66 pages

    Nasal Drug Delivery System

    Uploaded by

    warezisgr8
    The document discusses nasal drug delivery systems. Key points include: - Nasal delivery provides a non-invasive alternative to injections with rapid drug absorption and onset of effects. It avoids hepatic first-pass metabolism. - The nasal cavity offers a large mucosal surface area for drug absorption. Drugs are absorbed both locally and systemically via the olfactory neurons, blood vessels, or cerebrospinal fluid. - Nasal delivery is well-suited for peptides and other drugs susceptible to degradation, with bioavailability comparable to IV injection and lower side effects than oral administration.

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    Download as PPT, PDF, TXT or read online from Scribd
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    of 66

    Welcome!

    NASAL

    DRUG DELIVERY SYSTEM

    CONTENTS
    Novel Drug Delivery System

    Global trends in drug delivery systems


    Nasal Drug Delivery System Medical aspects Formulation Development Applications Conclusion

    NOVEL DRUG DELIVERY SYSTEM - an overview

    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%

    By 2010, the US drug


    delivery market alone will be worth $30 billion

    There are great opportunities for companies


    investing in R&D for new, improved drug delivery system, allowing for improved therapeutic absorption and efficacy in patients

    Why Novel Drug


    Delivery system? To optimize drugs therapeutic effect, convenience and dose To enhance a products life-cycle To improve `patient compliance

    To target drug delivery To control overall healthcare costs


    To facilitate biological drug delivery
    7

    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 therapeutics
    8

    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 diseases


    9

    Today there are between 300 & 350 companies worldwide with an interest in drug delivery, operating in a fierce 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
    10

    Drug Delivery Systems

    Oral

    Injectable

    Mucosal

    Topical

    Transdermal

    Ocular

    Vaginal/ Anal

    Needle Needleless

    Nasal Buccal Pulmonary

    Active Passive

    11

    Global drug delivery market by administration mode


    Nasal 2% Ocular 2% Injectable/ Implant 3% Transdermal 8% Inhalation 32% Oral 53%

    12

    13

    Inhalation/pulmonary drug delivery system includes


    Metered dose inhalers Dry powder inhalers Inhalation solutions & suspensions (for nebulizers) Inhalation nasal sprays

    14

    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

    15

    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 Limitations

    16

    30%

    11%

    Annual growth of locally acting products

    Annual growth of systemically acting products

    17

    Drug development time

    10 14 years

    New Chemical Entity

    2 5 years

    Nasal Drug Delivery

    18

    Drug development cost

    $300-600 mio

    New Chemical Entity

    $50 mio

    Nasal Drug Delivery

    19

    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

    20

    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.

    21

    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 bioavailability

    22

    23

    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 absorption

    24

    Cross-sectional view Nasal site of drug spray & absorption Pathways for nasal absorption

    25

    Cross-sectional view

    a nasal vestibule b palate c inferior turbinate

    d middle turbinate e superior turbinate (olfactory mucosa) f nasopharynx

    26

    Site of drug spray & absorption

    27

    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

    28

    Transneuronal absorption

    Olfactory nerve 1st cranial sensory nerve


    29

    Venous drainage

    30

    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 dehydrogenase
    31

    Nasal enzymes contd.,


    Progesterone and testosterone were metabolized by several steroid hydroxylases in the nasal mucosa of rats

    32

    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

    33

    34

    Therapeutic class of drugs


    1. 2 adrenergic agonists

    2. Corticosteroids
    3. Antiviral 4. Antibiotics 5. Antifungal 6. More recently, vaccines

    35

    Drugs commonly administered through pulmonary route include 1. Terbutaline Sulphate - 2 adrenergic agonist 2. Salbutamol - 2 adrenergic agonist

    3. Budesonide - corticosteroid
    4. Ipratropium Bromide - anticholinergic 5. Sodium Chromoglycate mast cell stabilizer

    36

    Formulation Development

    37

    Formulation Development Dosage form Factors affecting drug absorption Formulation considerations

    Physiological Pharmaceutical
    38

    Dosage forms

    Liquid drop Liquid spray/nebulizers Aerosol Suspension spray/nebulizers Gel Sustained release

    39

    Drug concentration

    Factors affecting drug absorption

    Vehicle of drug delivery Mucosal contact time Degree of drugs ionization pH of the absorption site Size of the drug molecule Relative lipid solubility
    40

    Physiological effects
    Drug metabolism in the respiratory tract &

    reduction of systemic effect


    Protein binding Mucociliary transport causing increased or decreased drug residence time

    41

    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

    42

    Pharmaceutical

    Physico-chemical properties of a drug candidate


    Methods to enhance drug absorption Spray pump devices

    43

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

    44

    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
    45

    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 used

    46

    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.
    47

    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 constant

    48

    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 drugs

    49

    5. Effect of drug concentration


    - Absorption depends on the initial concentration of

    the drug
    - The absorption follows first-order kinetics

    50

    Methods to enhance nasal absorption of drugs

    Structural modification
    Salt or ester formation Formulation design

    51

    SPRAY PUMP DEVICES

    - Unidose
    - Bidose - Multidose

    52

    Bidose Unidose
    53

    Multidose

    54

    LEADING PUMP SUPPLIERS


    Pfeiffer, Germany Valois, France Becton Dickinson, France Nemo, Spain

    55

    Applications
    Delivery of non-peptide pharmaceuticals

    Delivery of peptide-based pharmaceuticals

    Delivery of diagnostic drugs

    56

    1. 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%
    57

    2. Delivery of peptide-based pharmaceuticals


    Peptides & proteins have a generally low oral

    bioavailability because of their physico-chemical


    instability and susceptibility to hepatogastrointestinal first-pass elimination Eg. Insulin, Calcitonin, Pituitary hormones etc. Nasal route is proving to be the best route for such

    biotechnological products

    58

    3. Delivery of diagnostic drugs

    Diagnostic agents such as

    Phenolsulfonphthalein kidney function


    Secretin pancreatic disorders

    Pentagastrin secretory function of gastric acid

    59

    60

    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 drugs

    61

    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 effects

    62

    Attractive for delicate molecules allowing systemic administration

    without significant degradation

    63

    Nasal drug delivery system offers flexibility for multiple formulations ranging from nasal drop to suspension spray

    64

    Recent activities indicate a bright prospect for site-specific delivery of biotechnological products such as Insulin & other hormones

    65

    66

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