NASAL DRUG DELIVERY SYSTEM

NASAL DRUG DELIVERY SYSTEM : 

NASAL DRUG DELIVERY SYSTEM 1 MAK95

Inhalation/pulmonary drug delivery system includes : 

Inhalation/pulmonary drug delivery system includes  Metered dose inhalers  Dry powder inhalers  Inhalation nasal sprays  Inhalation solutions & suspensions (for nebulizers) 2 MAK95

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. Historically, nasal drug delivery system has received interest since ancient times 3 MAK95

Merits : 

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 MAK95

Merits... : 

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 MAK95

Limitations : 

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 6 MAK95

NASAL ROUTE- medical aspects : 

NASAL ROUTE- medical aspects 7 MAK95

Slide 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 absorption 8 MAK95

Slide 9: 

Cross-sectional view Nasal site of drug spray & absorption Pathways for nasal absorption 9 MAK95

Cross-sectional view : 

Cross-sectional view a – nasal vestibule d – middle turbinate b – palate e – superior turbinate (olfactory mucosa) c – inferior turbinate f – nasopharynx 10 MAK95

Slide 11: 

Site of drug spray & absorption 11 MAK95

Pathways for nasal absorption : 

Pathways for nasal absorption  Absorption through the olfactory neurons - transneuronal absorption. Olfactory epithelium is considered as a portal for substances to enter CNS  Absorption into the cerebrospinal fluid  Absorption through the supporting cells & the surrounding capillary bed - venous drainage 12 MAK95

Transneuronal absorption : 

Transneuronal absorption Olfactory nerve – 1st cranial sensory nerve 13 MAK95

Nasal enzymes : 

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 14 MAK95

Nasal enzymes – contd., : 

Nasal enzymes – contd., Progesterone and testosterone were metabolized by several steroid hydroxylases in the nasal mucosa of rats. 15 MAK95

Nasal pH : 

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 16 MAK95

Therapeutic class of drugs for nasal route : 

Therapeutic class of drugs for nasal route 17 MAK95

Therapeutic class of drugs : 

Therapeutic class of drugs 1. 2 adrenergic agonists 2. Corticosteroids 3. Antiviral 4. Antibiotics 6. More recently, vaccines 5. Antifungal 18 MAK95

Drugs commonly administered through pulmonary route include : 

Drugs commonly administered through pulmonary route include 1. Terbutaline Sulphate - 2 adrenergic agonist 2. Salbutamol - 2 adrenergic agonist 4. Ipratropium Bromide - anticholinergic 5. Sodium Chromoglycate – mast cell stabilizer 3. Budesonide - corticosteroid 19 MAK95

Slide 20: 

Formulation Development 20 MAK95

Slide 21: 

Formulation Development Dosage form Formulation considerations Factors affecting drug absorption Physiological Pharmaceutical 21 MAK95

Dosage forms : 

Dosage forms Liquid drop Liquid spray/nebulizers Aerosol Suspension spray/nebulizers Gel Sustained release 22 MAK95

Slide 23: 

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 23 MAK95

Physiological effects : 

Physiological effects Drug metabolism in the respiratory tract & reduction of systemic effect Protein binding - Mucociliary transport causing increased or decreased drug residence time 24 MAK95

Physiological effects.... : 

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 carriers 25 MAK95

Pharmaceutical effects : 

Pharmaceutical effects Physico-chemical properties of a drug candidate - Spray pump devices Methods to enhance drug absorption 26 MAK95

Slide 27: 

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 27 MAK95

Methods to enhance nasal absorption of drugs : 

Methods to enhance nasal absorption of drugs Structural modification Salt or ester formation Formulation design 28 MAK95

SPRAY PUMP DEVICES : 

SPRAY PUMP DEVICES Unidose Bidose Multidose 29 MAK95

Applications : 

Applications Delivery of non-peptide pharmaceuticals Delivery of peptide-based pharmaceuticals Delivery of diagnostic drugs 30 MAK95

Delivery of non-peptide pharmaceuticals : 

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 MAK95

Delivery of peptide-based pharmaceuticals : 

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 products 32 MAK95

Delivery of diagnostic drugs : 

Delivery of diagnostic drugs Diagnostic agents such as  Phenolsulfonphthalein – kidney function  Secretin – pancreatic disorders  Pentagastrin – secretory function of gastric acid 33 MAK95

CONCLUSION : 

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 drugs 34 MAK95

Slide 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 effects 35 MAK95

Slide 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 spray 36 MAK95

Slide 37: 

Recent activities indicate a bright prospect for site-specific delivery of biotechnological products such as Insulin & other hormones 37 MAK95

THANK YOU : 

THANK YOU E-mail: mail2mak49@yahoo.co.in 38 MAK95