Recommended
More Related Content
Similar to NDDS.pptx
Similar to NDDS.pptx (20)
Recently uploaded
Recently uploaded (20)
NDDS.pptx
- 1. NASAL DRUG DELIVERY SYSTEM BY:- Priti Mittal (210121220015) Masters of Pharmacy (Pharmaceutics) GJUS&T, Hisar, Haryana
- 2. TABLE OF CONTENTS 01 02 03 04 INTRODUCTION THERAPEUTIC CLASS OF DRUG AND EXAMPLE PHYSICO-CHEMICAL PROPERTIES OF DRUG METHODS TO ENHANCE NASAL ABSORPTION OF DRUG 05 GENERAL FORMULATION TYPES OF DDS 09 10 DOSAGE FORMS ADVANTAGES AND DISADVANTAGES APPLICATIONS 07 06 08 11 REFERENCES EVALUATION OF NASAL FORMULATION
- 4. INTRODUCTION Administration of drug through nasal route is referred as Nasal drug delivery system. Nasal route is an alternative to invasive administrations and provides a direct access to the systemic circulation. Intranasal Medication administration offers a truly “Needleless ” solution to drug delivery. In recent years many drugs have been shown to achieve better systemic bioavailability through nasal route than by oral administration. Nasal therapy, has been recognized form of treatment in the Ayurvedic systems of Indian medicine, it is also called “NASAYA KARMA”.
- 6. Therapeutic class of drugs 6. More recently, vaccines 3. Antiviral 1. Beta-2 adrenergic agonists 2. Corticosteroids 4. Antibiotics 5. Antifungal
- 7. The respiratory tract, which includes the ● nasal ● mucosa ● Hypo pharynx ● large airways ● small airways provides a relatively large mucosal surface area of approx. 100 m2 (in normal adult) for drug absorption
- 8. Drugs commonly administered through pulmonary route include Ipratropium Bromide - anticholinergic Budesonide - corticosteroid. Terbutaline Sulphate - Beta 2 adrenergic agonist Salbutamol - Beta 2 adrenergic agonist Sodium Chromoglycat e – mast cell stabilizer
- 11. Effect of molecular size - Higher the molecular size, lower the nasal absorption - A good systemic bioavailability can be achieved formolecules with a molecular weight of up to 1000Daltons when no absorption enhancer is used. - With the assistance of absorption enhancer, a goodbioavailability can be extended to a molecular weight of at least 6000 Daltons. -Absorption enhancers: Polyacrylic acidSodium GlycocholateSodium Deoxycholate
- 12. Effect of solution pH dissociation constant (pKa) of the molecule - Nasal absorption is pH dependent - Absorption is higher at a pH lower than the dissociation constant (pKa) of the molecule - Absorption is lower as the pH increases beyond the dissociation constant
- 13. Effect of drug lipophilicity - Polar (water soluble) drugs tend to remain on the tissues of the upper airway - Non-polar (lipid soluble) drugs are more likely to reach distal airways - Lipid soluble drugs are absorbed more rapidly than water soluble drugs
- 14. Effect of drug concentration - Absorption depends on the initial concentration of the drug - The absorption follows first-order kinetics
- 15. Dosage Forms 04 LIQUID DROP LIQUID SPRAY/NEBULIZER AEROSOL SUSPENSION SPRAY/NEBULIZER GEL SUSTAINED RELEASE
- 16. Nasal drops are one of the most convenient & simple systems for nasal delivery. These are instilled into the nose by dropper. Aqueous or oily solutions, since the latter inhibit the movement of cilia in the nasal mucosa . if used for longer periods , may reach the lungs &cause lipoid pneumonia. nasal drops should be isotonic having neutral pH & viscosity similar to nasal secretions by using methyl cellulose. E.g.:- ephedrine nasal drops B.P.C, otrivine nasal drops. Nasal drops
- 17. These are aqueous or alcoholic preparations. Applied to the mucous membrane of nose by atomizer. Only fine droplets are required so they may reach the lungs. By using metered pumps & actuators a nasal spray can deliver an exact µm. e.g.:- adrenaline & atropine spray B.P.C Nasal Spray
- 18. This dosage form may be developed if solution & suspension dosage forms cannot be developed e.g due to lack of drug stability .The powder formulation is dependent on the solubility ,particle size , aerodynamic properties &nasal irritancy of the active drug & or excipients. E .g:- sinu air nasal powder Nasal Powder
- 19. These are high viscosity thickened solutions or suspensions. Nasal gels include the reduction of post-nasal drip due to high viscosity , reduction of taste impact due to reduced swallowing, reduction of anterior leakage of formulation, reduction of irritation by using soothing /emollient excipients & target to mucosa for better absorption. Nasal Gels
- 20. 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 Nasal Vaccines
- 22. Methods to enhance nasal absorption of drugs 05 Structural modification Salt or ester formation Formulation design
- 23. General formulation Drug Preservatives Viscosifying agent Solubilizers Antioxidents BIOADHESIVE POLYMERS
- 24. DRUGS Drugs commonly used are; 1. β2-adrenergic agonist: terbutaline sulphate. 2. Corticosteroids : budesonide 3. Anti cholinergic: ipratropium bromide 4. Mast cell stabilizer : sodium chromogylate.
- 25. Factors affecting drug absorption Drug concentration Vehicle of drug delivery Mucosal contact time Degree of drug’s ionization pH of the absorption site Size of the drug molecule Relative lipid solubility
- 26. VISCOSIFYING AGENTS These agents increase the viscosity of the solution prolonging the therapeutic activity of preparation. e.g.: hydroxypropyl cellulose.
- 27. SOLUBILIZERS Aqueous solubility of drug always a limitation for nasal drug delivery. e.g.: glycol, alcohol, labrasol, transcutol. In such cases surfactants or cyclodextrines (HP- β -cyclodextrine) are used , these serve as a biocompatible solubilizer & stabilizer in combination with lipophilic absorption enhancers.
- 28. SURFACTANTS Modify the permeability of nasal mucosa & facilitate the nasal absorption of drugs. E.g. SLS, Poly acrylic acid, sod. glycocholate.
- 29. BIOADHESIVE POLYMERS Increases the residence time of drug in nasal cavity and a higher local drug concentration in the mucus lining on the nasal mucosal surface E.g.: Methylcellulose, Carboxymethylcellulose Hydroxyl propyl cellulose
- 30. PRESERVATIVES These are used to prevent the growth of micro organisms. e.g.: parabens, benzalkonium chloride, phenyl ethyl alcohol, EDTA etc.
- 31. ANTIOXIDANTS These are used to prevent drug oxidation. E.g.: sodium meta bisulphite , sodium bisulfite, butylated hydroxy toluene& tocopherol etc.
- 32. ABSORBTION ENHANCERS (a) Surfactants Sodium glycocholate Sodium deoxycholate (b) Chitosan (c) Cyclodextrins Hydroxypropyl-ß-cyclodextrin Dimethyl-ß-cyclodextrin (d) Complexing agents EDTA Citric acid . (e) Fatty acid salts Oleic acid Caprylic acid Lauric acid (f) Phospholipids L-α- lysophosphatidyl choline (g) Fusidates Sodium taurodihydrofusidate
- 34. In Vivo Nasal Absorption studies Animal models for nasal absorption studies The animal models employed for nasal absorption studies can be of two types, viz., whole animal or in vivo model and an isolated organ perfusion or ex vivo model, 1.RAT MODEL 2.RABBIT MODEL 3.DOG MODEL 4.SHEEP MODEL
- 35. Rat Model The rat is anaesthetized by intraperitoneal injection of sodium pentobarbital. An incision is made in the 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.
- 36. 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.
- 37. 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.
- 38. 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.
- 39. 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. In summary rat & rabbit are small, easy to handle & low in cost & inexpensive to maintain. In rat limitation application because of small body & size hence only useful for preliminary studies of nasal drug absorption.
- 40. ADVANTAGES 08
- 41. 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 Studied so far carried out indicate that the nasal route is an alternate to parenteral route, especially, for protein and peptide drugs. Convenient for the patients, especially for those on long term therapy, when compared with parenteral medication. Drugs possessing poor stability in G.I.T. fluids are given by nasal route. Polar compounds exhibiting poor oral absorption may be particularly suited for this route of delivery.
- 42. DISADVANTAGES 09
- 43. 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. Nasal cavity provides smaller absorption surface area when compared to GIT. There is a risk of local side effects and irreversible damage of the cilia on the nasal mucosa, both from the substance and from constituents added to the dosage form. Certain surfactants used as chemical enhancers may disrupt and even dissolve membrane in high concentration.
- 44. Applications 10
- 45. Delivery of non peptide pharmaceuticals Delivery of non-peptide pharmaceuticals 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%
- 46. 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 E.g. . Insulin, Calcitonin , Pituitary hormones etc. Nasal route is proving to be the best route for such biotechnological products
- 47. Delivery of diagnostic drugs Delivery of diagnostic drugs Diagnostic agents such as Phenolsulfonphthalein – kidney function. Secretin – pancreatic disorders Pentagastrin – secretory function of gastric acid
- 48. Delivery of Vaccines The nasal mucosa is the first site of contacts 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. Many diseases, such as Measles , pertussis , meningitis and influenza are associated with the entry of pathogenic microorganisms across the respiratory mucosal surfaces and are hence good candidates for nasal vaccines.
- 50. Thank you😃