Introduction to Naso-pulmonary Drug Delivery System (Part-I), Unit-III, BP704T: NDDS, Sem-VII, Final Year B. Pharm (SPPU 2019P).pptx

Unit III
Nasopulmonary drug delivery system: Introduction to Nasal and Pulmonary routes of
drug delivery, Formulation of Inhalers (dry powder and metered dose), nasal sprays,
nebulizers.

1. UNIT III Transdermal Drug Delivery Systems: Introduction, Permeation through skin, factors affecting permeation, permeation enhancers, basic components of TDDS, formulation approaches. Gastro-Retentive Drug Delivery Systems: Introduction, advantages, disadvantages, approaches for GRDDS - Floating, high density systems, inflatable & gastro-adhesive systems & their applications. Naso-Pulmonary Drug Delivery Systems: Introduction to Nasal & Pulmonary routes of drug delivery, Formulation of Inhalers (dry powder & metered dose), nasal sprays, nebulizers. 2

2. NASO-PULMONARY DRUG DELIVERY SYSTEMS (NPDDS) Ms. Kartiki M. Bhandari Assistant Professor (Pharmaceutics)

3. INTRODUCTION to Nasal DDS In ancient times, the Indian Ayurvedic system of medicines used nasal route for drug administration & the process is k/a “ Nasya .” Intra-nasal DDS is now recognized to be a useful & reliable alternative to oral & parenteral routes for controlled / sustained release . This route additionally seems to be favourable way to circumvent obstacles of Blood-Brain Barrier (BBB) allowing direct delivery of drug in CNS . Also useful in formulating nasal vaccines .

4. INTRODUCTION to Nasal DDS For many years, drugs have been administered nasally for both topical & systemic action. Topical administration includes treatment of congestion, rhinitis, sinusitis & nasal allergies such as - decongestants for cold nasal symptoms & anti-histamines & corticosteroids for allergic rhinitis. Intranasal is effective in systemic delivery with faster & extended absorption than oral / IV routes. For ex. analgesics (morphine); cardio-vascular drugs (propranolol, carvedilol); hormones (levonorgestrel, progesterone, & insulin); anti‐inflammatory agents (indomethacin, ketorolac); & antiviral drugs (acyclovir).

5. INTRODUCTION to Nasal DDS Potential route to achieve faster & higher level of drug absorption because it is permeable to more compounds than GIT due to lack of pancreatic & gastric enzymatic activity , neutral pH of the nasal mucus & less dilution by GI contents. Useful for drugs that are active in low doses & show minimal oral bioavailability . But low degree of absorption of peptides & proteins via nasal route is seen due to rapid removal away from absorption site in the nasal cavity due to muco-ciliary clearance (MCC).

6. INTRODUCTION to PULMONARY DDS Recent approach to treat both local & systemic lung diseases. Deliver the drug to the required site directly or to other distant sites through bloodstream . Lungs provide huge surface area of alveoli with rich capillary network, which acts as an excellent absorbing surface for drug. Since several years, rapid onset of action & higher efficiency has been responsible for success of PDDS for symptomatic relief in treatment of asthma & COPD.

7. INTRODUCTION to PULMONARY DDS Treatment efficacy depends on drug delivery technique & optimum drug conc ., above or below this range can be toxic or produce no therapeutic benefits (Therapeutic window). Slow progress in efficacy of treatment has suggested growing need for multi-disciplinary approach to deliver therapeutic agents to targets in tissues. Efficacy is achieved by controlling PK-PD, immunogenicity, & bio-recognition . These new interdisciplinary approaches - polymer science, P’ceutical technology, bio-conjugate chemistry, molecular biology are c/a “ novel / advanced drug delivery systems ”.

8. INTRODUCTION to PULMONARY DDS PDDS has become an attractive target in healthcare research area as lungs are capable of absorbing pharmaceuticals either for local deposition or for systemic delivery. Respiratory epithelial cells have prominent role in regulation of airway tone & production of airway lining fluid. In this respect, growing attention has been given to PDDS as a non-invasive approach for systemic & local delivery, because the high permeability & large surface area of lungs, (approx. 70-140 m² in adults with thin absorptive mucosal membrane) & good blood supply.

9. ANATOMY OF NASAL CAVITY Olfactory route Trigeminal route Pulmonary route

10. ADVANTAGES of npdds Drug degradation observed in the GIT is absent . Avoids hepatic 1 st pass metabolism . Rapid drug absorption & quick onset of action . Bioavailability of larger molecules can be improved by means of absorption enhancer or other approach. Nasal bioavailability for smaller drug molecules is good .

11. ADVANTAGES of npdds Drugs that are orally not absorbed can be delivered to systemic circulation by NDDS. Studies so far carried out indicate that nasal route is an alternate to parenteral route, especially, for protein & peptide drugs. Convenient in long term therapy as compared to parenterals. Drugs possessing poor stability in GI fluids are given by nasal route. Polar compounds exhibiting poor oral absorption may be suited for this route.

12. DISADVANTAGES of npdds Histo -toxicity of absorption enhancers used in NDDS is not yet clearly established. Inconvenient to patients as compared to oral systems due to possibility of nasal irritation. Nasal cavity provides smaller absorption surface area than GIT. Risk of local side effects & irreversible damage of cilia on the nasal mucosa, both from the drug & from excipients added to dosage form.

13. DISADVANTAGES of npdds Certain surfactants used as chemical enhancers may disrupt & even dissolve membrane in high conc. There could be mechanical loss of dosage form into other parts of respiratory tract like lungs; because of improper technique of administration. Loss of drug due to MCC . Hence, many absorption mechanisms were established; but only few used predominantly .

14. NASAL ABSORPTION MECHANISM Paracellular / Aqueous Route: Slow & passive absorption associated with intercellular spaces & tight junctions . Inverse log-log correlation between intranasal absorption & MW of H 2 O-soluble compounds. MW > 1000 Da  Poor bioavailability.

15. NASAL ABSORPTION MECHANISM Transcellular / Lipoidal Route: For transport of lipophilic drugs whose rate depends on lipophilicity. Drug also cross cell membranes by active transport route via carrier-mediated means or transport through opening of tight junctions. For example : chitosan, a natural biopolymer from shellfish, opens tight junctions between epithelial cells to facilitate drug transport. Transcytosis Route: Drug is taken into vesicle ( carrier ) & transferred to cell.

16. NASAL ABSORPTION MECHANISM

17. NASAL ABSORPTION MECHANISM Mucoadhesive NDDS:

18. FACTORS AFFECTING NASAL ABSORPTION Physiochemical properties of drug: Molecular size ( < 1000 Da ) Hydrophilic-lipophilic balance (HLB) Enzymatic degradation in nasal cavity Stability Solubility Physical & Chemical state of drug.

19. FACTORS AFFECTING NASAL ABSORPTION Nasal Effect: Membrane permeability Environmental pH ( normal pH of nasal cavity: 5.5 to 6.5 ) Muco-ciliary clearance (MCC) ( average MCC: 8.2 mins in children & 9.5 mins in adults ) Cold, rhinitis ( pH rises to 7.2 to 8.3 ) Blood flow.

20. FACTORS AFFECTING NASAL ABSORPTION Effect of drug formulation: Formulation (concentration, pH, osmolarity) Delivery effects / side effects Drugs distribution & deposition (protein binding) Viscosity Pharmaceutical excipients.

21. FORMULATION APPROACHES OF NPDDS Nasal drops Nasal gels Nasal powders Nasal sprays * Nasal inhalers * Nebulizers * Liposomes Microspheres “ * ” = In the syllabus

22. EVALUATION TESTS of npdds pH Osmolality Viscosity Impurities & degradation products Preservatives & stabilizing excipients assay Pump delivery Spray content uniformity (SCU) Spray pattern & plume geometry Droplet size distribution Particle size distribution 23 Osmolality: No. of moles of dissolved particles / kg of solution Plum: A quantity of smoke that arise in the air; Size & shape of plum is determined 80-120% of label claim should be delivered in each spray for 20 sprays studied (10 from beginning & 10 from end); no should deviate outside 75-125%; mean of all should not be outside of 85-115% of label claim For suspension only For solution & suspension 5.5-6.5 (7.2-8.3 in rhinitis) (mucus secretion: 95% H2O, 2% glycoproteins, 1% inorganic salts, <1% lipids) Limit test, DSC / IR UV, HPLC Brookfield, Ostwald

23. ANY QUESTIONS…???