Intranasal drug delivery system

intra nasal drug delivery system its introduction , preparation , evaluation

1. INTRA - NASAL DRUG DELIVERY SYSTEM PRESENTED BY : NISHA.N M PHARM 2 nd SEM DEPT. OF PHARMACEUTICS SUBMITTED TO : MRS. SUMA DEPT. OF PHARMACEUTICS MALLIGE COLLEGE OF PHARMACY

2. CONTENTS Introduction Formulation Nasal drug delivery dosage form Evaluation of nasal formulations Applications Reference

3. INTRODUCTION Generally nose is the important part of body for inhalation process. But when it is used as the route of drug delivery attained the great attraction for various drugs. Because nose provides faster and higher level of drug absorption with possibility of self-administration  . In present era, nasal drug delivery system has been considered as potential and favourable route of drug delivery because it provides patient compliance, easy to administration, bypass first pass metabolism, excellent penetration, low dose required, rapid absorption and gives desirable effects

4. DEFINITION : Intranasal drug delivery is a useful delivery method for drugs that are active in low doses and show no minimal oral bioavailability such as proteins and peptides . Nasal administration is a route of administration in which the drugs are insufflated through the nose for either local or systemic effect .

5. S. NO. ADVANTAGES FACTORS 1. Improving patient compliance Needle free (painless) Trained person not required 2. Good penetration in case of lipophilic drugs in case of low molecular weight 3. rapid absorption and onset of action Due to relative large surface area High vascularisation ADVANTAGES

6. 4. Avoidance of the harsh environment less chemical and enzymatic degradation 5. low dose required Free from first pass metabolism 6. Direct delivery of drug to central nervous system via olfactory region, thus bypass the blood brain barrier

7. DISADVANTAGES SL . NO LIMITATIONS FACTORS 1. Risk of local side effect and irreversible damage of cilia on nasal mucosa due to constituents added to dosage forms 2. Disrupt and even dissolve the nasal membrane Due to high concentration of absorption enhancers 3. Reduce the capacity of nasal absorption Due to nasal atrophic rhinitis and severe vasomotor rhinitis 4. Low bioavailability due to enzymatic degradation and metabolism at mucosal surface.

8. FORMULATION 1) BUFFERS : Isotonic potassium phosphate buffer Citrate buffer Acetate buffer 2) OSMOTIC AGENTS : Sodium chloride Sodium sulphite Sodium acid phosphate 3) GELLING / VISCOSIFYING AGENTS : Carbopol Cellulose agents Starch

9. 4) SOLUBILIZERS : Glycols Small quantities of alcohol Surfactants 5) PRESERVATIVES : Parabens Benzalkonium chloride Benzoyl alcohol 6) ANTI-OXIDANTS : Sodium metabisulphite Sodium bisulphite 7) HUMECTANTS : Glycerine Sorbitol Mannitol

10. 8) ABSORPTION ENHANCERS : (a) Surfactants Sodium glycocholate (b) Chitosan (c) Cyclodextrins Hydroxypropyl -ß- cyclodextrin (d) Complexing agent s EDTA (e) Fatty acid salts Oleic acid Lauric acid ( f) Phospholipids L- α- lysophosphatidyl choline

11. NASAL DRUG DELIVERY DOSAGE FORMS CLASSIFICATION : Liquid nasal formulations a) Instillation & Rhinyle catheter b) Compressed air nebulizers c) Squeezed nasal bottle d) Metered-dose pump sprays 2) Powder dosage forms a) Insufflators b) Dry powder inhaler 3) Pressurized metered dose inhalers 4) Nasal gels 5) Nasal vaccines

12. 1 ) LIQUID NASAL FORMULATION • Liquid preparations are the most widely used dosage forms for nasal administration of drugs. • They are mainly based on aqueous state formulations. • Their humidifying effect is convenient and useful, since many allergic and chronic diseases are often connected with crusts and drying of mucous membranes.

13. a) Instillation & Rhinyle catheter : Catheters are used to deliver the drops to a specified region of nasal cavity easily. • Place the formulation in the tube and kept tube one end was positioned in the nose, and the solution was delivered into the nasal cavity by blowing through the other end by mouth .

14. b ) Compressed air nebulizers : • Nebulizer is a device used to administer medication in the form of a mist inhaled into the lungs. • The compressed air is filling into the device, so it is called compressed air nebulizers.

15. Squeezed nasal bottles : Squeezed nasal bottles are mainly used as delivery device . • They include a smooth plastic bottle with a simple jet outlet .

16. d) Metered-dose pump sprays : Most of the pharmaceutical nasal preparations on the market containing solutions, emulsions or suspensions are delivered by metered-dose pump sprays. • Nasal sprays, or nasal mists, are used for the nasal delivery of a drug or either locally to generally alleviate cold or allergy symptoms such as nasal Congestion .

17. 2 ) Powdered dosage forms : a) Insufflators : Dry powders are less frequently used in nasal drug delivery. • Powder dosage form may be devoleped if solution & suspension dosage form cannot be devoleped . Eg: due to lack of drug stability . • Major advantages of this dosage form are the lack of preservatives and the improved stability of the formulation.

18. b) DRY POWDER INHALER : • Dry powder inhalers (DPIs) are devices through which a dry powder formulation of an active drug is delivered for local or systemic effect via the pulmonary route. • These are commonly used to treat respiratory diseases such as asthma, bronchitis, emphysema and COPD .

19. 3) PRESSURIZED METERED DOSE INHALERS • A metered-dose inhaler (MDI) is a device that delivers a specific amount of medication to the lungs, in the form of a short burst of aerosolized medicine that is inhaled by the patient .

20. NASAL GELS • Nasal gels are high-viscosity thickened solutions or suspensions. • The advantages of a nasal gel include the reduction of post-nasal drip due high viscosity, reduction of taste impact due to reduced swallowing, of anterior leakage of the formulation,reduction of irritation by using soothing/emollient excipients and target delivery to mucosa for better absorption

21. NASAL VACCINES • Nasal mucosa is the first site of contact with inhaled antigens and therefore , it is used for respiratory infections. • Nasal vaccination is a promising alternative to the parentral route , because is able to enhance the systemic levels of specific immunoglobulin G & nasal secretary immunoglobulin A. Eg : Nasal vaccines against influenza A & B Virus

22. EVALUATION OF NASAL FORMULATIONS Rat model • sodium pentobarbital ( i.p .). • neck and the trachea is cannulated with a polyethylene tube. • Another tube is inserted through the oesophagus towards the posterior region of the nasal cavity. • The passage nasopalatine tract is sealed so that the drug solution is not drained from the nasal cavity through the mouth. • The drug solution is delivered to the nasal cavity through the nostril or through the cannulation tubing. • Femoral vein is used to collect the blood samples.

23. Rabbit Model • Rabbits (approx. 3 kg) anaesthetized by i.m . injection of a combination of ketamine and xylazine . • The rabbit's head held in upright position and nasal spray administered into each nostril. • The blood samples collected by an indwelling catheter in the marginal ear vein or artery. In vitro diffusion studies • Nasal mucosa of sheep separated from sub layer bony tissues. • After complete removal of blood from mucosal surface, attached to donor chamber tube. • The donor chamber tube placed such a way that it just touches the diffusion medium in recipient chamber. • Samples (0.5 ml) from recipient chamber withdrawn at predetermined intervals.

24. APPLICATIONS 1) LOCAL DELIVERY • Oxymetazoline (Nasal spray), Xylometazoline (Nasal spray, nasal drops), Ephedrine (Nasal drops) – Symptomatic relief of nasal congestion. • Azelastine , Levocabastine , Olapatadine (Nasal spray) - Seasonal and perennial allergic rhinitis and non-allergic perennial rhinitis. • Fluticasone , Beclomethasone dipropionate , Mometasone , Triamcinolone acetonide (Nasal spray, suspension)- Seasonal and perennial allergic rhinitis and non-allergic perennial rhinitis. • Cromolyn sodium (Nasal spray, suspension) - Symptomatic prevention and treatment of seasonal or perennial rhinitis. • Neomycin sulfate (Nasal Cream) – Nasal infection.

25. 2) NASAL VACCINES • Especially against respiratory infections. • important against HIV and Hepatitis B virus. • Live attenuated influenza vaccine ( FluMist ) – Nasal Spray Suspension. (attenuated respiratory syncytial virus and parainfluenza 3 virus). 3) CNS DELIVERY • Delivery of drugs to CNS; impenetrable nature of BBB. • Alzheimer’s disease • Tumors (5-FU) • Epilepsy (diazepam, carbamazepine ) • Pain ( chitosan -morphine) • Antimicrobial ( cephalexin )

26. REFERENCE : NASAL DRUG DELIVERY SYSTEM: A COMPLETE REVIEW By dharmendra kumar and Sumedh Bansali https://www.slideshare.net/AlexaJacob1/intranasal-drug-delivery-system https://www.slideshare.net/DrSahilKumar/intranasal-route-of-drug-administration