pulmonary drug delivery system, mpharm sem 2

The PowerPoint presentation titled "Advances in Pulmonary Drug Delivery Systems" explores the evolving landscape of inhalation therapies designed to enhance therapeutic efficacy through targeted inhalation. It begins with an introduction to the fundamentals of pulmonary drug delivery, highlighting its significance in achieving localized treatment and minimizing systemic side effects. The presentation discusses three primary types of delivery systems: Metered Dose Inhalers (MDIs), Dry Powder Inhalers (DPIs), and Nebulizers, detailing their mechanisms, advantages, and clinical applications. Key benefits such as rapid onset of action and improved patient compliance are emphasized, along with challenges such as device technique and formulation stability. Solutions and innovations in device technology, formulation strategies, and patient-centric design are also addressed, reflecting advancements aimed at overcoming existing barriers. The presentation concludes by outlining future trends in personalized medicine, digital health integration, and emerging research areas like nanotechnology and biologics, underscoring the potential impact on enhancing patient outcomes across various therapeutic areas.

1. PULMONARY DRUG DELIVERY SYSTEM PRESENTED BY HATASHA VADDADI ERN:2308422110004 1 ST YR , M.PHARM(PHARMACEUTICS) SCHOOL OF PHARMACY,PARUL UNIVERSITY

2. TABLE OF CONTENT INTRODUCTION FORMULATION APPROACHES HISTORY OF PDDS CONCLUSION PHYSIOLOGICAL FACTORS REFERENCES

3. INTRODUCTION Pulmonary route used to treat different respiratory diseases from ancient times Inhalation therapies involved the use of leaves from plants, vapours from aromatic plants, balsams, and myrrh. Pulmonary drug delivery is primarily used to treat conditions of the airways, delivering locally acting drugs directly to their site of action. Delivery of drugs directly to their site of action reduces the dose needed to produce a pharmacological effect. Presentation By Samira Hadid

4. INTRODUCTION The respiratory tract is one of the oldest routes used to administer drugs. In Ayurveda diseases associated with breathing are mentioned in Sahasajanya Rajayakshma of Charak Samhita Over the past decades inhalation therapy has established itself as a valuable tool in the local therapy of pulmonary diseases such as asthma or COPD Presentation By Samira Hadid

5. HISTORY OF PDDS •In the 1920s adrenaline was introduced as a nebulizer solution. •Porcine insulin nebulizer (in 1925) was first brought into use for conducting experimental studies on diabetes. •Pulmonary delivery of penicillin was a subject of investigation in mid-1940s, while steroids have been in existence for treating Asthma since around 1955.

6. MECHANISM OF PARTICLE DEPOSITION IN THE AIRWAYS •Inertial impaction •Sedimentation •Diffusion

7. PHYSIOLOGICAL FACTORS AFFECTING PARTICLE DEPOSITION IN THE AIRWAYS •Lung morphology •Inspiratory flow rate •Co-ordination of aerosol generation with inspiration •Tidal volume •Breath holding •Disease states

8. PHARMACEUTICAL FACTORS AFFECTING AEROSOL DEPOSITION Aerosol velocity Size Shape Density Physical stability

9. ADVANTAGES Less invasive. Enhanced patient compliance. Localized drug deposition reduces incidence of systemic and generalized exposure. Avoidance of first pass metabolism. Rapid onset of action due to quick absorption across the mucous membrane. Easy of formulation of water insoluble/ soluble drug molecules. Avoidance of gastrointestinal upset.

10. DISADVANTAGES Low efficiency and low amount of drugs delivered per puff. Targeting problems. Poor formulation stability of drugs. Immunogenicity problems with protein based drug. Rapid drug clearance by phagocytosis and mucociliary clearance. Aerosol devices can be difficult to use Various factors affect the reproducibility of drug delivery to the lungs, including physiological (respiratory maneuver) and pharmaceutical (device, formulation) variables.

11. FORMULATION APPROACHES •Pulmonary delivered drugs are rapidly absorbed except large macromolecules drugs, which may yield low bioavailability due to enzymatic degradation and/or low mucosal permeability. •Pulmonary bioavailability of drugs could be improved by including various permeation enhancers such as surfactants, fatty acids, and saccharides, chelating agents and enzyme inhibitors such as protease inhibitors. •The most important issue is the protein stability in the formulation

12. NEBULIZER •A nebulizer is a device used to administer medication to patient in the form of a mist inhaled into the lungs •It is commonly used in treating cystic fibrosis, asthma, and other respiratory diseases There are two basic types of nebulizers: • The jet nebulizer functions by the Bernoulli principle by which compressed gas (air or oxygen) passes through a narrow orifice, creating an area of low pressure at the outlet of the adjacent liquid feed tube. This results in the drug solution being drawn up from the fluid reservoir and shattering into droplets in the gas stream. • The ultrasonic nebulizer uses a piezoelectric crystal, vibrating at a high frequency (usually 1-3 MHz), to generate a fountain of liquid in the nebulizer chamber; the higher the frequency, the smaller the droplets produced

13. INDICATIONS FOR NEBULIZER •Useful in children •Handicapped person •Seriously ill patients •Ventilated patients • Elderly individuals

14. ADVANTAGES •Enhancement of secretion clearance •Sputum induction •Humidification of respired gases •Prevent dehydration •Prevent or relieve bronchospasm

15. DRUGS FOR NEBULIZATION •Distilled water or normal saline •Mucolytics : mesna , acetylcysteine •Beta 2 agonists: salbutamol, terbutalin , fometerol , salmeterol •Antimuscarinics : ipratropium bromide •Steroids: budesonide •Antibiotics

16. AEROSOLS Aerosol preparations are stable dispersions or suspensions of solid material and liquid droplets in a gaseous medium. The drug delivery by aerosols is deposited in the airways by: gravitational sedimentation, inertial impaction, and diffusion. Mostly larger drug particles are deposited by first two mechanisms in the airways, while the smaller particles get their way into the peripheral region of the lungs by following diffusion. • There are three commonly used clinical aerosols: 1. Jet or ultrasonic nebulizers, 2. Metered-dose Inhaler (MDI) 3. dry-powder inhaler (DPI) The basic function of these three completely different devices is to generate a drug-containing aerosol cloud that contains the highest possible fraction of particles in the desired size range.

17. ADVANTAGES OF AEROSOLS •Easily withdrawl of drug •Easy and convenient to apply. •Faster Onset of action. •No manual/ direct contact with the medicament. •Avoid the first pass metabolism. •A specific amount of dose or drug can be removed. •No microorganism can enter. •Release the contents in Controlled and Uniformly.

18. DISADVANTAGES OF AEROSOLS •Costly. •Difficult disposal of empty aerosol containers. •Allergic in some cases. •Explosive. •Patient Compliance is Highly Necessary •Sometimes propellants may cause toxic reactions •Proper technique is needed to take dose effciently

19. METERED DOSE INHALERS (MDI) •Used for treatment of respiratory diseases such as asthma and COPD. •They can be given in the form of suspension or solution. •Particle size of less than 5 microns. •Used to minimize the number of administrations errors. •It can be deliver measure amount of medicament accurately.

20. ADVANTAGES OF MDI •It delivers specified amount of dose. •Small size and convenience. •Usually inexpensive as compare to dry powder inhalers and nebulizers. •Quick to use. •Multi dose capability more than 100 doses available.

21. DISADVANTAGES OF MDI •Difficult to deliver high doses. • There is no information about the number of doses left in the MDI. •Accurate co-ordination between actuation of a dose and inhalation is essential.

22. •DPIs are bolus drug delivery devices that contain solid drug in a dry powder mix (DPI) that is fluidized when the patient inhales. •DPIs are typically formulated as one-phase, solid particle blends. The drug with particle sizes of less than 5µm is used •Dry powder formulations either contain the active drug alone or have a carrier powder (e.g. lactose) mixed with the drug to increase flow properties of drug. •DPIs are a widely accepted inhaled delivery dosage form, particularly in Europe, where they are currently used by approximately 40% of asthma patients. DRY POWDER INHALERS (DPI)

23. ADVANTAGES Propellant-free. Less need for patient co-ordination. Less formulation problems. Dry powders are at a lower energy state, which reduces the rate of chemical degradation.

24. DISADVANTAGES Dependency on patient's inspiratory flow rate and profile. Device resistance and other design issues. Greater potential problems in dose uniformity. More expensive than pressurized metered dose inhalers. Not available worldwide

25. TYPES OF DRY POWDER INHALERS •Unit-Dose Devices •Single dose powder inhalers are devices in which a powder containing capsule is placed in a holder. The capsule is opened within the device and the powder is inhaled. • Mulitidose Devices •This device is truly a metered-dose powder delivery system. The drug is contained within a storage reservoir and can be dispensed into the dosing chamber by a simple back and forth twisting action on the base of the unit.

26. MARKETED FORMULATIONS

27. RECENT ADVANCES IN PDDS •The Aerogen Pulmonary Delivery Technology

28. RECENT ADVANCES IN PDDS SPIROS INHALER TECHNOLOGY

29. Metered Dose Inhalers Market Outlook 2031 According to the World Health Organization (WHO), 235 million people globally suffer from asthma, and 64 million people suffer from COPD. These numbers are expected to rise in the next few years, with asthma projected to affect around 400 million people by 2025 and COPD projected to be the third leading cause of death worldwide by 2030. Metered Dose Inhalers Market Outlook 2031 The global industry was valued at US$ 16.3 Bn in 2021 It is projected to grow at a CAGR of 3.1% from 2022 to 2031 and reach more than US$ 22.1 Bn by 2031

30. CONCLUSION The various approaches for efficient and targetted drug delivery to the pulmonary mucosa for systemic and local provide an essential way to alleviate various chronic and acute diseased states As emerging pharmaceutical systems develop further care should be taken to ensure patient compliance and the need for counselling and tutoring for appropriate technique to take dose in proper manner. The Pulmonary DDS have saved millions worldwide from death by their easily approachable method of drug delivery although there is still room for development leaving scope for formulation scientists to further provide pioneering methods for drug delivery.

31. REFERENCES •Jain N. K, "Advances in Controlled and Novel Drug Delivery" 1st ed. (2010), CBS Publishers and Distributors Pvt.Ltd . New Delhi, pp.120-156. Groneberg , D.A., Witt, C., Wagner, U., Chung, K.F. and Fischer, A., 2003. Fundamentals of pulmonary drug delivery. Respiratory medicine, 97(4), pp.382-387. Patil, J.S. and Sarasija , S., 2012. Pulmonary drug delivery strategies: A concise, systematic review. Lung India: Official Organ of Indian Chest Society, 29(1), p.44. Liang, Z., Ni, R., Zhou, J. and Mao, S., 2015. Recent advances in controlled pulmonary drug delivery. Drug Discovery Today, 20(3), pp.380-389. Taylor, T.E., Zigel , Y., Egan, C. et al. Objective Assessment of Patient Inhaler User Technique Using an Audio-Based Classification Approach. Sci Rep 8, 2164 (2018). https://doi.org/10.1038/s41598-018-20523-w