pulmonary drug delivery system

about pdds and its recent technology

1. Pulmonary drug delivery system: a novel approach for drug delivery Presented by: Rana Harshraj A. Guide by: Dr. Mittal Maheshwari M. Pharm (Pharmaceutics) A One Pharmacy College

2. Content: Introduction, Anatomy and physiology of lungs, Advantage and disadvantage of pulmonary drug delivery system, Aerosol, propellant & container types, Current technology for pulmonary drug delivery, New technology for pulmonary drug delivery, Evaluation of pharmaceutical aerosol & PDDS.

3. Introduction: Pulmonary drug delivery is primarily used to treat condition of the airway, delivering locally acting drug directly to their site of action. Delivery of anti-asthmatic and other locally acting drug directly to their site of action reduce the dose needed to produce a pharmacological effect, while the low concentration in the systemic circulation may also reduce side effect. The drug which are administered by pulmonary route are not only for lungs delivery but it goes to systemic circulation and produce the effect where it is desired through out the body. A product containing ergotamine tartrate is available as an aerosolized dosage inhaler for the treatment of migraine & volatile anaesthetic, halothane, are also given via the pulmonary route.

4. Introduction: (Continue) The pulmonary route has gained increasing importance in the recent times due to its unique properties such as a large absorptive area of up to 100m2 ; extremely thin 0.1μm – 0.2μm absorptive mucosal membrane and good blood supply. Devices used to deliver drug by pulmonary route area based on one of three platforms pressurized metered dose inhaler, nebulizer and dry powder. Pulmonary route processes many advantages over other routes of administration for the treatment of specific disease states, particularly lung associated large protein molecules which degrade in the gastrointestinal conditions and are eliminated by the first pass metabolism in the liver can be delivered via the pulmonary route if deposited in the respiratory zone of the lung. Pulmonary routes have been used to treat various respiratory diseases for century. Ancient inhalation therapy includes the use of leave from plants, vapors from aromatic plat, balsam and myrrh . In the 1920 adrenalin was introduce as the nebulizer solution , in 1925 nebulizer porcine insulin was use in experimental studies in diabetes, and in 1945 pulmonary delivery recently discover penicillin was investigate. Steroid had been introduced in mid-1950 for the treatment of asthma and nebulizer enjoy wide spread use. In 1956 the pressure metered inhaler (PMDI) was introduce , over the past 5 decades , helped by advance in molecules design and drug discovery the PMDI has risen to become the main stay of asthma treatment.

5. Introduction: (Continue) Over the decades certain drugs have been sold in compositions suitable for forming drug dispersion for pulmonary delivery to treat various conditions in humans. Such pulmonary drug delivery compositions are designed to be delivered by inhalation by the patient of drug dispersion so that the active drug within the dispersion can reach the lung. It has been four that certain drugs given by pulmonary route are readily absorbed through the alveolar region directly into blood circulation. pulmonary route possesses many advantages over other routes of administration for the treatment of specific disease states, particularly lung associated large protein molecules which degrade in the gastrointestinal conditions and are eliminated by the first pass metabolism in the liver can be delivered via the pulmonary route if deposited in the respiratory zone of the lung by fascinating the systematic delivery of large and small molecules drugs through inhalation deep into the lung, this advanced pulmonary technology provides unique and innovative delivery alternative for therapies that must currently be administered by injection (I.V, I.M, S.C.) or by oral delivery that causes adverse effects or is poorly absorbed.

6. Introduction: (Continue) New dispersible formulations and drug aerosol delivery devices for inhalable peptides, proteins, and various small molecules have in the past decade. Become of increasing interest for the treatment of systemic or respiratory diseases. these include, but also extend well beyond, the traditional and long available (although still underutilized) therapies for asthma and chronic obstructive pulmonary disease (COPD) advances in the use of the lungs as portals for delivery of medication to the blood stream have greatly expanded the potential applications of pulmonary delivery. This advances technology was initially applied to the systematic delivery of large molecules, such as insulin, interferon-b, or a1 proteinase inhibitor.

7. Anatomy and physiology of lungs: Lungs region Nasopharyngeal region Tracheo-bronchial region Alveolar region

8. Continue: 1) Lungs region: The respiratory tract start at the nose and terminate in the lung at an alveolar sac. There are a number of schemes for categorizing the various region of the respiratory tract. 2) Nasopharyngeal region: (NP region) This is also referred to as the upper airway, which involve the respiratory airway from the nose down to the larynx.

9. Continue: 3) tracheo-bronchial region: (TB region) This is also referred to as the central or conducting airway, which start at the larynx and extend via the trachea, bronchi, bronchiole and end at the terminal bronchiole. 4) Alveolar region: This is also referred to as the respiratory, peripheral airway or pulmonary region, comprising the respiratory bronchiole, alveolar duct and alveoli.

10. Drug administered by inhalation for local action in airway (COPD) drugs diseases examples B2-adrenoceptor agonists Asthma, COPD Salbutamol, terbutaline, fenoterol, salmeterol. Corticosteroids Asthma, COPD Budesonide, beclomethasone. Anticholinergics Asthma, COPD Ipratropium bromide Anti-inflammatory Asthma Nedocromil, cromoglycate

11. Advantages of PDDS: Inhaled drug delivery puts drugs where it is needed. It requires low and fraction of oral dose I.e. drug content of one 4 mg tablet of salbutamol equal to 40 dose of meter doses. Pulmonary drug delivery having very negligible side effect since rest of body is not exposed to drug. Onset of action is very quick with pulmonary drug delivery. Degradation of drug by liver is avoided in pulmonary drug delivery. in asthma and diabetes requires long term treatment if it is given by pulmonary drug delivery safety is maximum because rest of body is not exposed to drug.

12. Disadvantage of PDDS. Low efficiency of inhalation system. Poor formulation stability for drug. Improper dosing reproducibility.

13. Aerosols & its components: Aerosol is a pressurized dosage form containing one or more therapeutic active ingredient which upon actuation emit a fine dispersion of liquid and/or solid material in a gaseous medium. 1. propellant 2. container 3. valve and actuator 4. product concentrate

14. Aerosol: Advantage : A dose can be removed without contamination of remaining material. The medication can be delivered directly to the affected area in a desired form such as spray or stable form. Irritation produced by mechanically application of topical medication is reduced or eliminated. Minimum contamination. Maximum stability. Disadvantage: ► poor patient compliance. ► increase bronco constriction. ► irritant activity. ► high cost of mfg..

15. Propellant: Single or blend of various propellant are used. It is selected to give the desired vapour pressure, solubility & particle size. Propellant can be with active ingredient in many different ways producing product with varying characteristics. Depending on the type of aerosol system utilized, the pharmaceutical aerosol may be dispensed as fine mist, wet spray & semi-solid or solid.

16. Method of inhalation drug delivery: Aerosol Pulmonary metered dose inhaler (PMDI) Dry powder inhaler (DPI) nebulizer

17. Metered dose inhaler: (MDI) Is a device that help to deliver a specific amount of medication to the lung. It is commonly used to treat asthma, chronic obstructive diseases. (COPD) It is composed of 4 essential components: The base formulation:- drug, propellent, excipient. The container. The metering valve. The actuator. (mouth piece)

18. Propellant: Commonly CFC propellant are used because of their low pulmonary toxicity, high chemical stability, purity and compatibility, non-inflammable. But now a day the cfc propellant are replaced with hydrofluoroalkanes (HFA) as these CFC cause the ozone depletion effect. Example: 1,2, dichlorotetrafluromethane. dichlorodifluoromethane. trichlorofluoromethane.

19. Surfactant: These are added to maintain the drug in dispersed state & promotes stability of formulation. It is also lubricant the valve. Example: oleic acid, sorbitol

20. Container: Usually the container is made up of aluminum or glass. Glass container are normally plastic coated or laminated to enhance their ability to ensure internal pressures of high magnitude.

21. Valve and its components: valve body and housing stem gasket spring Dip tube Metering valve: These are designed to release a fixed volume of product during each actuation. Usually valve volume range from 25ml to 100ml although larger volume are available.

22. Dry powder inhaler: This device dispense a powder in stream of inspired air. These are environmentally friend since they do not required CFC propellant for drug dispersion. Self medication is possible. Two type of dry powder inhaler: A. passive dry powder inhaler: example: disc inhaler, easy inhaler. B. active dry powder inhaler: example: spiors, prohaler. C. Unit Dose Devices: D. Multi Unit Dose Device:

23. Dry powder inhaler: (continue) Advantage: Product and formulation stability. High drug volume delivery per puff. Low susceptibility to microbial growth. Applicable to both soluble and insoluble drug. Self medication is possible. Disadvantage: Hygroscopic powder have chance to particle growth. Accurate dose is required.

24. Nebulizer: Nebulizer are those that aerosolize aqueous solution of water soluble drug or suspension & solvent water based solution of water insoluble substance. Nebulizer have been successfully employed for drug delivery to the lung. It is also used for local drug delivery to trachea for local anaesthesia. there are two type of nebulizer: A. pneumatic nebulizer:- it derives from pressurized gas source. Example: jet or hydro dynamic type B. electrical nebulizer:- it operate from an electric source. Example: ultra sonic nebulizer

25. Therapeutic application of PDDS: For the treatment of asthma Pulmonary infection For chronic obstructive pulmonary disease Cardio vascular agent Blood glucose modifier Lung cancer Cystic fibrosis

26. List of marketed product: Ventolin ► Liposomes Asmol ► Lactose Carrier Systems Albuterol sulfate ► Biodegradable Polymers Salbutamol ► Nano Aerosols. Liposomal Formulation:- Insulin, Catalase, Ciprofloxacin, Interleukin-2 (IL-2), Rifampicin, Nitrocamptothecin (9-NC), Budesonide, Ketotifen fumarate. Drug-Loaded Nanoparticles:- Protein, Cisplatin, Mometasone furoate, Rifampicin. Drug Loaded Microspheres:- Albumin microspheres , Chitosan/b-cyclodextrin microspheres, Polyethylene glycol, Gelatine microspheres, Poly-lactic glycolic acid (PLGA).

27. CURRENT TRENDS IN PULMONARY DRUG DELIVERY: 1. Particle Engineering for Pulmonary Drug Delivery 2. Agglomerated Vesicle Technology for Pulmonary Drug Delivery 3. Metered Dose Inhalers (MDI) 4. Dry Powder Inhalers (DPI) 5. Air Classifier Technology in Devices 6. Nebulizers 7. Nano Aerosols 8. Liposomes 9. Lactose Carrier Systems 10. Large Porous Particles 11. Biodegradable Polymers 12. Reverse Micelles 13. Aerodynamically Light Particles for Pulmonary Drug Delivery

28. Thank you By:- Mr. rana harshraj a.