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Nasal drug delivery 2
Intranasal drug delivery offers a needleless solution for drug administration. The nasal cavity provides a large mucosal surface area for drug absorption. Drugs commonly delivered intranasally include beta-agonists, corticosteroids, antibiotics, and vaccines. Formulations include liquids, sprays, gels, and powders. Factors like particle size, pH, and drug properties influence nasal absorption. This non-invasive route is useful for delivering peptides, proteins, and diagnostic agents with its direct access to the systemic circulation.
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Nasal drug delivery 2
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- 2. IntroductIon Intranasal Medicationadministration offers a truly “Needleless” solution to drug delivery. Therapy through intranasal administration has been an accepted a form of treatment in the Ayurvedic system of Indian medicine 2
- 3. Merits 3
- 4. 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 4
- 5. TE U L RO ts S A spec N A a ic al ed -m 5
- 6. • The respiratorytract, 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 6
- 7. Cross-sectional view Nasal siteof drug spray & absorption Pathways for nasal absorption 7
- 8. Cross-sectional view a –nasal vestibule d – middle turbinate b – palate e – superior turbinate (olfactory mucosa) c – inferior turbinate f – nasopharynx 8
- 9. Site of drug spray & absorption 9
- 10. Pathways for nasalabsorption 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 10
- 11. nose braIn pathway The olfactory mucosa (smelling area in nose) is in direct contact with the brain and CSF. Medications absorbed across the olfactory mucosa directly enter the brain. This area is termed the nose brain pathway and offers a rapid, direct route for drug delivery to the brain. Olfactory mucosa Brain CSF Highly vascular nasal mucosa 11
- 12. Nasal pH •Nasal secretionof 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 12
- 13. of ss t e la u c ic l r o ut sa pe na r a or he s f T g dru 13
- 14. Therapeutic class ofdrugs 1. β2 adrenergic agonists 2. Corticosteroids 3. Antiviral 4. Antibiotics 5. Antifungal 6. More recently, vaccines 14
- 15. Drugs commonly administeredthrough 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 stabilizer 15
- 16. Formulation Development Dosage form Dosage form Factors affecting drug Factors affecting drug absorption absorption Formulation considerations Formulation considerations Physiological Pharmaceutical 16
- 17. Dosage forms Liquid drop Liquid spray/nebulizers Aerosol Suspension spray/nebulizers Gel Sustained release 17
- 18. Drug concentration Factors affecting pH of the absorption site drug absorption Size of the drug particle Relative lipid solubility Mucosal contact time Molecule weight of the drug 18
- 19. Factors Affecting Bioavailability Deliverysystem characteristics: Nasal mucosal surface area coverage: • Larger surface area delivery = higher bioavailability. Particle size: • Particle size 10-50 microns adheres best to the nasal mucosa. • Smaller particles pass on to the lungs, larger particles form droplets and run-out of the nose. 19
- 20. cont.. Atomizationresults in higher bioavailability than either spray or drops. For this reason, nasal pharmaceuticals come with atomized drug delivery systems. 20
- 21. Physiological effects - Drugmetabolism in the respiratory tract & reduction of systemic effect - Protein binding - Mucociliary transport causing increased or decreased drug residence time 21
- 22. 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 22
- 23. Methods to enhancenasal absorption of drugs Structural modification Salt or ester formation Formulation design 23
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- 25. Bidose Multidose Unidose 25
- 26. Nasal Drops Nasal dropsare one of the most simple and convenient systems developed for nasal delivery. The main disadvantage of this system is the lack of the dose precision and therefore nasal drops may not be suitable for prescription products. It has been reported that nasal drops deposit human serum albumin in the nostrils more efficiently than nasal sprays. 26
- 27. Nasal sprays Both solution and suspension formulations can be formulated into nasal sprays. Due to the availability of metered dose pumps and actuators, a nasal spray can deliver an exact dose from 25 to 200 μm. The particles size and morphology(for suspensions)of the drug and viscosity of the formulation determine the choice of pump and actuator assembly. 27
- 28. Lincoln Pharma winspatent for a novel nasal drug delivery system • Presently in India anti-vomiting treatments are available in the conventional form of tablet and injection which take longer time to bring relief. • But now through LPL’s new Nasal Drug Delivery System, the patient can get immediate relief. LPL becomes the first company in India to introduce an anti-vomiting treatment in the form of a Nasal spray pump.
- 29. • Stem CellNasal Spray for Parkinson Disease Significantly Improves Motor Function Successful intranasal delivery of stem cells to the brains of rats with Parkinson disease yielded significant improvement in motor function and reversed the dopamine deficiency characteristic of the disease. This was reported as a Rejuvenation Research in journal published by Mary Ann Liebert.
- 30. Mucosal Atomization Device (MAD) – Device designed to allow emergency personnel to delivery nasal medications as an atomized spray. – Broad 30-micron spray ensure excellent mucosal coverage.
- 31. Nasal Powder This dosageform may be developed if solution and suspension dosage forms cannot be developed e.g., due to lack of drug stability. The advantages to the nasal powder dosage form are the absence of preservative and superior stability of the formulation. Local application of drug is another advantage of this system. Nasal powder formulation depends on the solubility, particles size, aerodynamic properties and nasal irritancy of the active drug and /or excipients. 31
- 32. Nasal Gels Nasal gelsare high-viscosity thickened solutions or suspensions. Advantages of a nasal gel Reduction of post-nasal drip due to high viscosity, Reduction of taste impact due to reduced swallowing, Reduction of anterior leakage of the formulation, Reduction of irritation by using soothing/emollient excipients and target to mucosa for better absorption. 32
- 33. Nasal vaccines Nasal mucosais first site of contact with inhaled antigens and, therefore, its use for vaccination, especially against respiratory infections Nasal vaccination is a promising alternative to the classic parenteral route, because it is able to enhance the systemic levels of specific immunoglobulin G and nasal secretary immunoglobulin A. Examples of human efficacy of intranasal vaccines include those against influenza A and B virus, proteosoma influenza. Denovirusvectored influenza and parainfluenza virus Intra nasal H1N1 vaccine Nasovac by Serum Institute 33
- 34. Current systemic therapeutics delivered nasally Desmopressin for diabetes mellitus Calcitonin for osteoporosis Sumatriptan for migraines Nascobal for pernicious anemia
- 35. Nasal Drug Deliverymedications Drugs of interest in Intranasal systems: Intranasal naloxone (Narcan) Intranasal midazolam (Versed) 35
- 36. Intranasal (IN) Naloxone Absorption of Intranasal naloxone almost as fast as IV in both animal and human models “Atomization” of medications show much better absorption via the Intranasal route 36
- 37. Examples of IntranasalDrug Delivery Systems Intranasal sustained-release formulation – Nasal absorption with Clofilium tosylate, enkephalin analogs – Short biological half-life Tobispray – Dry, metered-dose nasal aerosol – Vasoconstrictor (tramazoline), steroid (dexamethasone isonicotinate), antibiotic (neomycin sulfate) Other examples are : Butorphanol, calcitocin, sumatriptan, Insulin, Vaccine and brain targeting drugs. 37
- 38. Cont… Efficacy ofcocaine by oral and intranasal administration – Nasal : detect in plasma by 15 min, peak concentration at 60 to 120 min, decrease gradually over the next 2 to 3h – Oral : not detected until 30 min, increased rapidly for the next 30 min In vivo absorption of sulbenicillin, cephacetrile, cephazoline – Oral : poor absorption because of high water solubility – Intranasal : ½ of im injection (% excretion in the urine ) 38
- 39. Market product otrivin spray(xylometazoline) miacalcin spray (calcitonin) vibrocil gel (phenylephrine,dimethindene maleate ) naset-p (xylometazoline HCL)-nasal drop nasovac H1N1 vaccine 39
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- 41. Applications Delivery ofnon-peptide pharmaceuticals Delivery of peptide-based pharmaceuticals Delivery of diagnostic drugs 41
- 42. 1. Delivery ofnon-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% 42
- 43. 2. Delivery ofpeptide-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 43
- 44. 3. Delivery ofdiagnostic drugs Diagnostic agents such as • Phenolsulfonphthalein – kidney function • Secretin – pancreatic disorders • Pentagastrin – secretory function of gastric acid 44
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