Nasal Drug Delivery System recent

NASAL DRUG DELIVERY SYSTEM: 

NASAL DRUG DELIVERY SYSTEM Desai paresh M.Pharm sem-2 Atmiya institute of pharmacy, rajkot 1 paresh desai

Introduction : 

Introduction Intranasal Medication administration 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 paresh desai

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Merits 3 paresh desai

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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 paresh desai

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NASAL ROUTE - medical aspects 5 paresh desai

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The respiratory tract, which includes the nasal mucosa hypopharynx large airways & small airways provides a relatively large mucosal surface area of approx. 100 m 2 (in normal adult) for drug absorption 6 paresh desai

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Cross-sectional view Pathways for nasal absorption Nasal site of drug spray & absorption 7 paresh desai

Cross-sectional view: 

Cross-sectional view a – nasal vestibule d – middle turbinate b – palate e – superior turbinate (olfactory mucosa) c – inferior turbinate f – nasopharynx 8 paresh desai

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Site of drug spray & absorption 9 paresh desai

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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 10 paresh desai

Nose brain pathway: 

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 Highly vascular nasal mucosa Brain CSF 11 paresh desai

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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 Nasal pH 12 paresh desai

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Therapeutic class of drugs for nasal route 13 paresh desai

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Therapeutic class of drugs 1.  2 adrenergic agonists 2. Corticosteroids 3. Antiviral 4. Antibiotics 6. More recently, vaccines 5. Antifungal 14 paresh desai

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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 15 paresh desai

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Formulation Development Dosage form Formulation considerations Factors affecting drug absorption Physiological Pharmaceutical 16 paresh desai

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Dosage forms Liquid drop Liquid spray/nebulizers Suspension spray/nebulizers Gel Sustained release Aerosol 17 paresh desai

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Factors affecting drug absorption Drug concentration Mucosal contact time pH of the absorption site Size of the drug particle Relative lipid solubility Molecule weight of the drug 18 paresh desai

Factors Affecting Bioavailability: 

Factors Affecting Bioavailability Delivery system 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 paresh desai

Cont..: 

Cont.. Atomization results in higher bioavailability than either spray or drops. For this reason, nasal pharmaceuticals come with atomized drug delivery systems. 20 paresh desai

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Physiological effects - Drug metabolism in the respiratory tract & reduction of systemic effect - Mucociliary transport causing increased or decreased drug residence time - Protein binding 21 paresh desai

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Physiological effects.... - Local or systemic effects of propellants, preservatives, or carriers - Local toxic effects of the drug Eg., edema, cell injury, or altered tissue defenses 22 paresh desai

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Methods to enhance nasal absorption of drugs Structural modification Formulation design Salt or ester formation 23 paresh desai

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SPRAY PUMP DEVICES 24 paresh desai

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Bidose Unidose Multidose 25 paresh desai

Nasal Drops : 

Nasal Drops Nasal drops are 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 paresh desai

Nasal sprays: 

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 paresh desai

Lincoln Pharma wins patent for a novel nasal drug delivery system : 

Lincoln Pharma wins patent 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. 28 paresh desai

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Stem Cell Nasal 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. 29 paresh desai

Mucosal Atomization Device (MAD): 

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. 30 paresh desai

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Nasal Powder This dosage form 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 paresh desai

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Nasal Gels Nasal gels are 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 paresh desai

Nasal vaccines: 

Nasal vaccines Nasal mucosa is 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 paresh desai

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Current systemic therapeutics delivered nasally Desmopressin for diabetes mellitus Calcitonin for osteoporosis Sumatriptan for migraines Nascobal for pernicious anemia 34 paresh desai

Nasal Drug Delivery medications : 

Nasal Drug Delivery medications Drugs of interest in Intranasal systems: Intranasal naloxone ( Narcan ) Intranasal midazolam (Versed) 35 paresh desai

Intranasal (IN) Naloxone: 

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 paresh desai

Examples of Intranasal Drug Delivery Systems: 

Examples of Intranasal Drug 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 paresh desai

Cont…: 

Efficacy of cocaine 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 ) Cont… 38 paresh desai

Market product otrivin spray (xylometazoline) miacalcin spray (calcitonin) vibrocil gel (phenylephrine,dimethindene maleate ) naset-p (xylometazoline HCL)-nasal drop nasovac H1N1 vaccine : 

Market product otrivin spray (xylometazoline) miacalcin spray (calcitonin) vibrocil gel ( phenylephrine,dimethindene maleate ) naset-p (xylometazoline HCL)-nasal drop nasovac H1N1 vaccine 39 paresh desai

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Leading pump suppliers 40 paresh desai

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Applications Delivery of non-peptide pharmaceuticals Delivery of diagnostic drugs Delivery of peptide-based pharmaceuticals 41 paresh desai

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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% 42 paresh desai

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2. 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 Eg. Insulin, Calcitonin, Pituitary hormones etc. Nasal route is proving to be the best route for such biotechnological products 43 paresh desai

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3. Delivery of diagnostic drugs Diagnostic agents such as  Phenolsulfonphthalein – kidney function  Secretin – pancreatic disorders  Pentagastrin – secretory function of gastric acid 44 paresh desai

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THANK YOU 45 paresh desai