logging in or signing up nasal drug delivery vvishu Download Post to : URL : Related Presentations : Let's Connect Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Copy embed code: Embed: Flash iPad Dynamic Copy Does not support media & animations Automatically changes to Flash or non-Flash embed WordPress Embed Customize Embed URL: Copy Thumbnail: Copy The presentation is successfully added In Your Favorites. Views: 1010 Category: Education License: All Rights Reserved Like it (0) Dislike it (0) Added: September 26, 2011 This Presentation is Public Favorites: 0 Presentation Description No description available. Comments Posting comment... Premium member Presentation Transcript SEMINAR ON intranasal drug delivery: SEMINAR ON intranasal drug delivery BY V. VISHALA M.PHARMACY II SEMESTER 2011Slide 2: INTRODUCTION ANATOMY AND PHYSIOLOGY OF NASAL CAVITY FACTORS INFLUENCING NASAL DRUG ABSORPTION NOSE TO BRAIN DELIVERY INTRANASAL DELIVERY OF VACCINES INTRANASAL DELIVERY OF PEPTIDE AND PROTEINE DRUGS THERAPEUTIC AREAS SUTIABLE FOR INTRANASAL DELIVERY CONCLUSION REFERENCES CONTENTSSlide 3: In ancient times the Indian Ayurvedic system of medicines used nasal route for administration of drug and the process is called as “Nasya” Infact, nasal mucosa evolved in order to have a wide surface, large blood supply and efficient filtering system These features are exploited for local and systemic effective drug delivery Various proteins & peptides have shown a good bioavailability INTRODUCTIONSlide 4: Clinical testing of IN Morphine gluconate compared with traditional IM and oral products INTRODUCTIONSlide 5: Avoidance of hepatic first-pass metabolism Avoids degradation of drug in gastrointestinal tract, resulting from acidic or enzymatic degradation Rate of absorption is high compared to IV medication. Results in rapid absorption and onset of effect Non-invasive, Painless, needle-free administration mode Easily accessible (even easier to access than IM or IV sites) Self-medication is possible through this route ADVANTAGESSlide 6: Results in higher bioavailability thus uses lower dose & hence lower side effects Useful for both local & systemic drug delivery Direct transport into systemic circulation and CNS is possible Offers lower risk of overdose Drugs that are orally not absorbed can be delivered to the systemic circulation by nasal drug delivery. ADVANTAGESSlide 7: Adversely affected by pathological conditions (cold or allergies may alter significantly the nasal bioavailability) Irritation of nasal mucosa by drugs Volume that can be delivered into nasal cavity is restricted to 25–200 μ l Normal defense mechanisms like mucocillary clearance and ciliary's beating affects the permeability of drugs Enzymatic barrier to permeability of drugs Interspecies variability is observed in this route. Absorption enhancers cause irritation LIMITATIONS: Major functions of the nasal cavity are breathing and olfaction. Nasal vasculature is richly supplied with blood to fulfill the basic functions such as heating and humidification, mucociliary clearance and immunological functions. Relatively large surface area (~150 cm 2 ) because of the presence of ~400 microvilli per cell. It is divided by middle (or nasal) septum into two symmetrical halves, each one opening at the face through nostrils and extending posterior to the nasopharynx. NASAL CAVITY :ANATOMY, PHYSIOLOGYSlide 9: ANOTOMY OF HUMAN NASAL CAVITYSlide 10: Site of drug spray & absorptionSlide 11: HUMAN NASAL EPITHELIUM CHARECTERSTICSMECHANISM OF DRUG ABSORPTION: MECHANISM OF DRUG ABSORPTION Two mechanisms are found to be involved: The first mechanism which is lipophilicity dependent. Transcellular Process. Ex: Chitosan The second mechanism which is dependent on molecular weight. Paracellular Route. Ex: Sodium CromoglycateSlide 14: NASAL PHYSIOLOGICAL FACTORS Blood flow As the blood flow ate increases the amount of drug that reaches the general circulation also increases. Kao et al. stated that nasal absorption of dopamine was relatively slow and incomplete probably due to its own vasoconstrictor effect. Mucociliary clearance (MCC) One of the functions of the upper respiratory tract is to prevent noxious substances ( allergens , bacteria , viruses , toxins etc) from reaching the lungs . When such materials adhere to , or dissolve in the mucus lining of the nasal cavity , they are transported towards the nasopharynx for eventual discharge into the GIT. Clearance of this mucus and the absorbed / dissolved substances is called the MCC.ENZYMATIC DEGRADATION: ENZYMATIC DEGRADATION Drugs may metabolized in nasal cavity because of presence of broad variety of metabolic enzymes like…. Cytochrome P 450, Lactate dehydrogenase, Oxidoreductase, Hydrolase's, Esterase, lactic dehydrogenize, malic enzymes, lysosomal proteinases, steroid hydroxylases., etc., Proteolytic enzymes amino peptidase and proteases, plays role in calcitonin Insulin and desmopressin.Slide 17: PHYSICOCHEMICAL PROPERTIES OF DRUGS Molecular weight , Lipophilicity and pKa Lipophilic drugs well absorbed through transcellular mechanisms with nasal bioavailability near to 100%( lower than 1 kDa). Absorption of lipophilic drugs bigger than 1 kDa is significantly reduced. Nasal absorption of polar drugs is low and highly dependent of molecular weight. Solubility Drugs poorly soluble in water may require high doses may constitute a problem as allowable volume of drug solution is low for intranasal drug administrationSlide 18: FORMULATION FACTORS pH, Concentration, the pH of the nasal formulation should be adjusted to 4.5–6.5. Concentration gradient plays very important role in the absorption / permeation process of drug through the nasal membrane due to nasal mucosal damage. Viscosity A higher viscosity increases contact time between the drug and the nasal mucosa thereby increasing the time for permeation. At the same time, highly viscous formulations interfere with the normal functions like ciliary beating or mucociliary clearance and thus alter the permeability of drugs. Osmolarity Drug absorption can be affected by tonicity of the formulation. Shrinkage of epithelial cells has been observed in the presence of hypertonic solutions. Hypertonic saline solutions also inhibit or cease ciliary activity. Low pH has a similar effect as that of a hypertonic solution.Slide 19: Particle size of the droplet or powder If the particle size is <10 μm, then particles will be deposited in the upper respiratory tract, whereas if particle size is <0.5 μm then it will be exhaled. Size between 5–7 μm will be retained in the nasal cavity. Pharmaceutical excipients Area of nasal mucus membrane exposed Dosage form Device related factor Site and pattern of depositionSlide 20: NOVEL DRUG FORMULATIONS Liposomes They can effectively encapsulate small and large molecules with a wide range of hydrophilicity and pKa values . They enhance nasal absorption of peptides such as insulin and calcitonin by increasing their membrane penetration (attributed to the increasing nasal retention of peptides, protection of the entrapped peptides from enzymatic degradation ). Novel mucoadhesive multivesicular liposomes for transmucosal insulin delivery has been investigating. Lliposomal drug delivery systems were also reported as useful for influenza vaccine and non-peptide drugs such as nifedipine.Slide 21: MICROSPHERES Microspheres based on muco adhesive polymers (chitosan, alginate) present advantages for IN delivery. Micro spheres may also protect the drug from enzymatic metabolism. Wang et al. have investigated gelatin micro spheres as a IN delivery system for insulin . Positive results are found for nasal delivery of Metoclopramide micro spheres of alginate/chitosan Carbamazepine chitosan micro spheres Carvedilol alginate micro spheresSlide 22: New and developing approach to deliver drugs to the brain. Improved delivery to the brain via the IN route has been reported for some low-mol.wt drugs as well as therapeutic peptides and proteins . Nose to brain delivery has been reported either in humans or animal models of Alzheimer’s disease, brain tumors, epilepsy, pain and sleep disorders . Nose to the CNS may occur via olfactory neuro epithelium. Since central nervous bioavailability of drugs, transported by the olfactory-pathway is estimated to be 0.01% to 0.1%, only very potent drugs may reach therapeutic levels NOSE TO BRAIN DELIVERYSlide 23: Possible routes of transport between the nasal cavity and the brain and CSFSlide 24: Nasal mucosa houses lymphatic tissues involved in the first line defense against airborne microorganism. In humans the NALT is known as the Waldeyer´s Ring. Reasons for exploiting the nasal route for vaccine delivery. The nasal mucosa is the first site of contact with inhaled pathogens. The nasal passages are rich in lymphoid tissue. Creation of both mucosal and systemic immune responses. Low cost, patient friendly, non-injectable, safe. INTRANASAL DELIVERY OF VACCINESSlide 25: The majority of the invading pathogens enter the body via mucosal surfaces. Therefore, mucosal sites have a potential as first line of defense against entering pathogens. Nasal secretions are known to contain immunoglobulins (IgA, IgG, IgM, IgE), and neutrophils and lymphocytes in the mucosa . Nasal vaccine delivery stimulates the production of local secretary IgA and IgG Nasal vaccine systems based on live or attenuated whole cells, split cells, proteins or polysaccharides and with and without various adjuvant were investigating.Slide 26: The chitosan nasal delivery system has been tested for influenza, and diphtheria vaccine in various animal models and in man. Bioadhesive property and transient effect on the tight junctions of chitosan lead to an improved immune response. It has been reported that Ab levels were similar for IM conventional influenza vaccine and nasal administration of the chitosan-influenza vaccine. Due to its positive charge chitosan gets complexed with negatively charged DNA plasmids and self-assembling into nanparticulate systems for improved delivery of DNA. Nasal delivery of DNA plasmid expressing epitopes of respiratory syncytial virus (RSV) to produce an effective vaccine.Slide 27: Being hydrophilic polar molecules of relatively high molecular weight, are poorly absorbed across biological membranes with low bioavailability . This low uptake may adequate for some commercial products such as desmopressin and calcitonin ( 3432 Da, 3% (Novartis Pharmaceuticals, 2006). Novel formulation strategies Absorption enhancers Bioadhesive agents Absorption enhancing effect of different cyclo-dextrins (rats,rabbits), medium chain fatty acid (rats), sodium tauro-24, 25-dihydrofusidate (sheep) on intranasally administered insulin in rats and rabbits was observed. INTRANASAL DELIVERY OF PEPTIDE AND PROTEIN DRUGSSlide 28: Bioavailability of peptides and proteins administered IN in the presence of absorption enhancersSlide 29: Bioavailability of peptides and proteins administered IN in the presence of absorption enhancersSlide 30: NASAL DOSAGE FORMS Nasal Drops Simple and convenient systems . Disadvantage is the lack of dose precision. Nasal Sprays Both solution and suspension can be formulated into nasal sprays. They can deliver an exact dose of 25 to 200 µl by metered dose pumps and actuators. The choice of pump and actuator assembly depend on the particle size and morphology (for suspensions) and viscosity of the formulation. Solution and suspension sprays are preferred over powder sprays because powder results in mucosal irritation .Slide 31: Nasal Gels Nasal gels are high-viscosity thickened solutions or suspensions. Advantages 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 Nasal Powders If solution and suspension dosage forms cannot be developed e.g. due to lack of drug stability Advantages Absence of preservative Superior stability Local application Disadvantages Nasal mucosa irritation, metered dose deliverySlide 32: Common devices are Droppers Squeeze bottles Spray pumps / atomizers (Accuspray Nasal Atomizer, MAD (Mucosal Atomization Device, nasal) Gel applicators Nasal Nebulisers (Sinus Nebuliser Rhino Clear) Pressurized Metered Dose Inhalers (pMDIs) Nasal (Ex: Landmark ® ) Disposable Unit/Bi-dose dispensing devices Powder Dispensing Systems MAD NASAL DELIVERY DEVICESSlide 33: LEADING PUMP SUPPLIERSSlide 34: THERAPEUTIC AREAS SUTIABLE FOR INTRANASAL DELIVERYCONCLUSION : CONCLUSION The intranasal route is an alternative route for drug administration . It is expected that novel nasal products will continue to reach the market due to wide spread benefits of this route. Nasal products will include drugs for acute and long term diseases and also vaccines with better local or systemic protection against infections. From this route drugs can be directly target to the brain in order to attain a good therapeutic effect in CNS .Slide 36: “ Much has been investigated and much more are to be investigated for recent advancement of nasal drug delivery system”Slide 37: REFERENCES Costantino HR, Illum L, Brandt G, Johnson PH, Quay SC. Intranasal delivery: Physicochemical and therapeutic aspects. Int J Pharm , 2007; 337:1-24. Chien YW, Su KSE, Chang . S,Nasal systemic drug deliver, 2 nd edition, USA:Marcel Dekker;1989.1-38,89-97. Talegaonkar S, Mishra PR. Intranasal delivery: An approach to bypass the blood brain barrier . Indian J Pharmacol 2004; 36(3): 140-147 Arora P, Sharma S, Garg S. Permeability issues in nasal drug delivery. Drug Discov Today 2002; 7(18): 967-975 Illum L. Transport of drugs from the nasal cavity to the central nervous system . Eur J Pharm Sci 2000; 11: 1-18 Y.W. Chien , S.F. Chang, Intranasal drug delivery for systemic medication, Crit. Rev. Ther . Drug Carrier Syst. 4 (1987) 67 S. Hirai, T. Yashiki , T. Matsuzawa, H. Mima , Absorption of drugs from the nasal mucosa of rat, Int. J. Pharm. 7 (1981) 317–325. H.D. Kao, Enhancement of delivery of L- Dopa by the administration of it’s prodrugs via the nasal route, University of Kentucky, Lexington, Kentucky, 1995. .N. Geurkink , Nasal anatomy, physiology, and function, J Allergy Clin . Immunol . 72 (1983) 123 128. Illum L. Nasal drug delivery: possibilities, problems and solutions. J Control Release, 2003; 87:187-198. Illum L. Transport of drugs from the nasal cavity to the central nervous system. Eur J Pharm Sci , 2000; 11:1-18. http://www.ehow.com/nasal-spray http://www.valoispharma.com http://www.pfeiffer-group.comSlide 38: THANK YOU You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.