Intranasal drug delivery system

Intranasal drug delivery system

1. Nasal drug delivery system Presented By : Alexa Jacob M.Pharm 2 nd Sem Dept. Of Pharmaceutics St.Joseph’s College Of Pharmacy,cherthala Alappuzha,kerala 1

2. CONTENTS DEFINITION ADVANTAGES DISADVANTAGES FORMULATION NASAL DRUG DELIVERY DOSAGE FORMS EVALUATION REFERENCE 2

3. DEFINITION Nasal administration is a route of administration in which the drugs are insufflated through the nose for either local or systemic effect. 3

4. Advantages Drug degradation that is observed in the gastrointestinal tract is absent. Hepatic first pass metabolism is avoided. Rapid drug absorption and quick onset of action can be achieved . The bioavailability of larger drug molecules can be improved by means of absorption enhancer or other approach. The nasal bioavailability for smaller drug molecules is good. Drugs that are orally not absorbed can be delivered to the systemic circulation by nasal drug delivery. 4

5. DISADVANTAGES Nasal administration is primarily suitable only for potent drugs. Drugs for continuous & frequent administration may be less suitable because of harmful long term effects. Nasal administration has also been associated with a high variability in the amount of drug absorbed. The histological toxicity of absorption enhancers used in nasal drug delivery system is not yet clearly established. Relatively inconvenient to patients when compared to oral delivery systems since there is a possibility of nasal irritation & n asal cavity provides smaller absorption surface area when compared to GIT. 5

6. formulation 1) BUFFERS : Isotonic potassium phosphate buffer Citrate buffer Acetate buffer 2) OSMOTIC AGENTS : Sodium chloride Sodium sulphite Sodium acid phosphate 6

7. 3) GELLING / VISCOSIFYING AGENTS : Carbopol Cellulose agents Starch Dextran Chitosan 4) SOLUBILIZERS : Glycols Small quantities of alcohol Transcutol ( Diethylene glycol monoethyl ether) Medium chain glycerides Surfactants 7

8. 5) PRESERVATIVES : Parabens Benzalkonium chloride Phenyl ethyl alcohol Benzoyl alcohol 6) ANTI-OXIDANTS : Sodium metabisulphite Sodium bisulphite Butylated hydroxytoluene Tocopherol 7) HUMECTANTS : Glycerine Sorbitol Mannitol 8

9. 8) ABSORPTION ENHANCERS : (a) Surfactants Sodium glycocholate Sodium deoxycholate (b) Chitosan (c) Cyclodextrins Hydroxypropyl -ß- cyclodextrin Dimethyl-ß- cyclodextrin (d) Complexing agents EDTA Citric acid 9

10. (e) Fatty acid salts Oleic acid Caprylic acid Lauric acid (f) Phospholipids L- α - lysophosphatidyl choline (g) Fusidates Sodium taurodihydrofusidate 10

11. NASAL DRUG DELIVERY DOSAGE FORMS A. LIQUID NASAL FORMULATIONS 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. 11

12. 1) 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 12

13. 2) 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. 13

14. 3) SQUEEZED NASAL BOTTLE : Squeezed nasal bottles are mainly used as delivery device for decongestants. They include a smooth plastic bottle with a simple jet outlet. 14

15. 4) 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 drugs, either locally to generally alleviate cold or allergy symptoms such as nasal congestion. 15

16. B. POWDER DOSAGE FORMS 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. 16

17. 1) INSUFFLATORS : Insufflators are the devices to deliver the drug substance for inhalation. It can be constructed by using a straw or tube which contains the drug substance and sometimes it contains syringe also. The achieved particle size of these systems is often increased compared to the particle size of the powder particles due to insufficient deaggregation of the particles and results in a high coefficient of variation for initial deposition areas. 17

18. 2) 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. 18

19. C. 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. 19

20. D. 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 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 delivery to mucosa for better absorption. 20

21. E. 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 it is able to enhance the systemic levels of specific immunoglobulin G & nasal secretary immunoglobulin A. Eg : Nasal vaccines against influenza A & B Virus 21

22. EVALUATION A. IN-VITRO NASAL DIFFUSION STUDIES : 22

23. B. IN-VIVO NASAL ABSORPTION MODELS : 1) RAT MODEL 23

24. 2) RABBIT MODEL : Rabbit is anaesthetized by intramuscular injection of a combination of ketamine and xylazine . The rabbit's head is held in an upright position and the drug solution is administered by nasal spray into each nostril . The blood samples are collected by an indwelling catheter in the marginal ear vein. 24

25. 3) DOG MODEL : The dog is anaesthetized by intravenous injection of sodium thiopental and the anesthesia is maintained with sodium Phenobarbital . A positive pressure pump through a cuffed endotracheal tube gives the ventilation . The blood sampling is carried out from the jugular vein. 25

26. 4) SHEEP MODEL : Sheep model for studying nasal drug delivery is prepared using basically the same procedure as that described for dog model. Male in-house bred sheep are employed since they are free from nasal infections . Practical and suitable for investigating nasal delivery formulations . 26

27. 5) MONKEY MODEL : The monkey is tranquillized by intramuscular injection of ketamine hydrochloride or anaesthetized by intravenous injection of sodium Phenobarbital . The head of the monkey is held in an upright position and the drug solution is administered into each nostril. The blood samples are collected through an indwelling catheter in the vein. 27

28. C. EX-VIVO NASAL PERFUSION MODEL : 28

29. REFERENCE Controlled & Novel Drug delivery by N.K Jain ; Pg no : 235-267 Textbook of industrial Pharmacy by Shobha Rani R Hiremath ; Pg no : 60-71 https:/www.slideshare.net.in 29

30. 30