肺部给药英文课件.ppt

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1、PULMONARY DRUG DELIVERY,Tarun K.Mandal,Ph.D.,Pulmonary Drug Delivery,MISCELLANEOUS PREPARATIONS,Pulmonary Drug Delivery,AEROSOLSAerosols are defined as colloidal systems of very finely subdivided liquid or solid particles dispersed in and surrounded by a gas.,Pulmonary Drug Delivery,Classifications

2、of Aerosol Products:1.space sprays 2.surface coating 3.aerated sprays,Pulmonary Drug Delivery,1.Space sprays.Disperse the active ingredients as a finely divided spray with the particle no longer than 50 m in diameter.2.Surface coating.Disperse larger particle,generally produce a wet or course spray.

3、,Pulmonary Drug Delivery,3.Aerated sprays.Disperse medicated foams,vaginal foams,shaving cream.,Pulmonary Drug Delivery,Advantages of the Aerosol Dosage form:Minimum Contamination Maximum Stability Reduces the irritation;cooling effect Easy to control:physical form;particle size;dose Clean process;r

4、equire no wash-up,Pulmonary Drug Delivery,The aerosols are used in pharmacy for local or systemic delivery of drugs.The total sales of beta agonist and cromolyn sodium aerosols in the United States 1984 1988 Beta agonist$121,000,000$238,000,000 Cromolyn sodium$12,000,000$56,000,000.,Pulmonary Drug D

5、elivery,Aerosols for local(topical)treatment:1.Topical medication may be applied in a uniform thin layer to the skin,without touching the affected area2.Aerosols are also used in the diagnosis,prevention or control of lung disease,Pulmonary Drug Delivery,Aerosols for systemic treatment:Polypeptide d

6、rugs The advantages of therapeutic aerosols1.The drugs begin to act very rapidly 2.Smaller dose can be used than with oral or intravenous delivery3.Reduction in the incidence of systemic side effect.,Pulmonary Drug Delivery,OVERALL STRUCTURE AND FUNCTION OF THE RESPIRATORY TRACTFUNCTION:The primary

7、function of the respiratory tract is gas exchangeA secondary function is cleaning and humidifying of the incoming air to prevent damage of this vital organOnly delivery by breathing via mouth is considered for aerosol dosage forms.,Pulmonary Drug Delivery,STRUCTURE:Upper airways oropharynx and laryn

8、x Lower airways trachea which is followed by successive bifurcations into bronchi and bronchioli.terminal bronchioli then divide into respiratory bronchioli until the ultimate respiratory zone,the alveoli is reached.,Pulmonary Drug Delivery,BLOOD AND LYMPH FLOW IN THE RESPIRATORY TRACT Pulmonary vas

9、culature forms a separate circuit from the systemic circulation.The main pulmonary artery starts in the right ventricle,then it divides into two branches for the left and right lungs.Drugs absorbed into the pulmonary circulation will avoid the first-pass hepatic effect,although they could be metabol

10、ized in the respiratory tract.,Pulmonary Drug Delivery,PHYSICAL MECHANISMS OF PARTICLE DEPOSITION IN RESPIRATORY TRACT The three mechanisms of aerosol kinetics govern the majority of particle deposition within the respiratory tract.,Pulmonary Drug Delivery,1.INERTIAL IMPACTION:Particles of diameters

11、 ranging from a few microns to greater than 100.The inertia of an airborne particle will tend to cause it to travel in its initial path when the supporting airstream is suddenly deflected(turbinates,bifurcations).,Pulmonary Drug Delivery,2.SEDIMENTATION:Every particle allowed to fall in air will acc

12、elerate to a terminal settling velocity(v)where the force of gravity is balanced by the resistance of the air through which the particle is falling:,Pulmonary Drug Delivery,2 r2(d1-d2)g v=-9 nr=radius of the particle;d1=density of the particle;d2=density of air;n=viscosity of air;g=gravitational con

13、stant.,Pulmonary Drug Delivery,Factors that may increase particle deposition by sedimentation are:a)increase in particle size b)decrease in airflow(breath-holding or long slow breathing).,Pulmonary Drug Delivery,3.DIFFUSION:Particle deposition by diffusion or brownian motion predominates for very sm

14、all particles(5 or less)and occurs predominantly in the periphery of the lung(respiratory bronchiole and alveolus).,Pulmonary Drug Delivery,FACTORS AFFECTING DEPOSITION A wide range of other factors influences the deposition of aerosols within the respiratory tract.,Pulmonary Drug Delivery,1.MODE OF

15、 INHALATION:The most important features of inhalation are a)inhaled volumeb)flow ratec)breath holding pause maintained at end inspiration,Pulmonary Drug Delivery,2.AEROSOL PROPERTIES:The vital physical property of the aerosol itself is the aerodynamic diameter(the product of physical diameter and th

16、e square root of density).,Pulmonary Drug Delivery,aerodynamic diameter 2 m-deposition in the oropharynx-less reaches the most peripheral parts of the lungThe ideal size for a therapeutic aerosol should not be more than 5 m to penetrate into the tracheobronchial tree and smaller airways if periphera

17、l deposition is required.,Pulmonary Drug Delivery,AEROSOL FORMULATIONThe Aerosol Principle1.Product Concentrate2.Propellant,Pulmonary Drug Delivery,Product Concentrate1.Active Ingredients2.Antioxidants3.Surface Active Agent4.Solvent,Pulmonary Drug Delivery,Propellant Liquified GasMixtureExample:Fluo

18、rinated Hydrocarbon Nonliquified GasExample:Carbon Dioxide,Nitrogen,Nitrous OxideAdvantages of Nitrogen as Propellent:1.It is insoluble in the product concentrate2.It is an odorless and tasteless gas,Pulmonary Drug Delivery,The pressure of an Aerosol is critical to its performance.It can be controll

19、ed by:1.The type and amount of propellant2.Nature/Amount of the product concentrate,Pulmonary Drug Delivery,Space Sprays-85%PropellantSurface Sprays-30-70%PropellantAerated Sprays-6-10%PropellantBlends of the various liquified gas propellants are generally used.,Pulmonary Drug Delivery,AEROSOLS AND

20、RAOULTS LAW The vapor pressure of pure propellant 11(MW 137.4)at 210 C is p110=13.4 pounds/square inch(psi)and that of propellant 12(MW 120.9)is p120=84.9 psi.,Pulmonary Drug Delivery,A 50:50 mixture of gram weight of the two propellants consists of 50 gm 137.4 g mole-1=0.364 mole of propellant 11,a

21、nd 50 gm 120.9 g mole-1=0.414 mole of propellant 12.What is the partial pressure of propellants 11 and 12 in the mixture and what is the total vapor pressure of this mixture?,Pulmonary Drug Delivery,p11=n11/(n11+n12)p110=0.364/(0.364+0.414)(13.4)=6.27 psip12=n12/(n11+n12)p120=0.414/(0.364+0.414)(84.

22、9)=45.2psiThe total vapor pressure of the mixture is 6.27+45.2=51.5 psi,Pulmonary Drug Delivery,TOXICITYThe Physiologic Effect Must Be Considered.Fluorinated Hydrocarbons have a relatively low order of toxicity.Rapid and repeated use may exhibit Cardiotoxic Effect.Cardiac toxicity is likely to be a

23、problem only for the occasional adult or child who deliberately abuses his/her metered dose inhaler,apparently to satisfy a craving for fluorinated hydrocarbon.,Pulmonary Drug Delivery,AEROSOL SYSTEMSTwo-Phase SystemsLiquid Phase1.Liquified Propellant2.Product ConcentrateVapor Phase,Pulmonary Drug D

24、elivery,Three-Phase Systems1.Water immiscible liquid propellant 2.Highly aqueous product concentrate 3.Vapor phase.,Pulmonary Drug Delivery,Compressed Gas Systems Compressed,rather than liquefied,gases may be used to prepare aerosols.The pressure of the compressed gas contained in the headspace of t

25、he aerosol container forces the product concentrate up the dip tube and out of the valve.,Pulmonary Drug Delivery,FILLING OPERATIONSCool below their boiling pointsCompress the gas at room temp.,Pulmonary Drug Delivery,Cold Filling:The product concentrate&the propellant must be cooled to-300 to-400 d

26、eg FDisadvantageAqueous systems cannot be filled,water turns to ice at this low temp.,Pulmonary Drug Delivery,Pressure Filling:The product concentrate is quantitatively placed in the aerosol container.This method is used for most Pharmaceutical formulations(aerosols)Advantages:1.Less danger of moist

27、ure contamination 2.Less propellant is lost,Pulmonary Drug Delivery,Testing the Filled ContainersTest for leaks or weaknesses at 130 deg FProper function of the valveTest for particle size distributionTest for accuracy and reproducibility of dosage when using metered valve.,Pulmonary Drug Delivery,P

28、ackaging:Packaging is part of the manufacturing process,Pulmonary Drug Delivery,Labeling:Use warning labels whenever required.Avoid inhaling.Keep away from eyes or other mucous membranes.Contents under pressure.Do not puncture or incinerate container.Do not expose to heat or store at temp.above 120

29、deg F(49 deg C).Do not inhale directly.Deliberate inhalation of contents can cause death.,Pulmonary Drug Delivery,TYPES OF INHALATION DEVICEThere are three types of device in common use.METERED DOSE INHALERNEBULIZERDRY POWDERED INHALER,Pulmonary Drug Delivery,APPLICATION OF AEROSOL SYSTEMS:Formulati

30、on of products containing therapeutically active ingredients.Pharmaceutical Aerosol:It may be defined as an aerosol product containing therapeutically active ingredients dissolved,suspended,or emulsified in a propellant or a mixture of solvent and propellant and intended for oral or topical administ

31、ration or administration into body cavities.,Pulmonary Drug Delivery,SPRAYS:Sprays are aqueous or alcoholic or glycerin solutions in the form of course droplets or as finely divided solids to be applied topically,most to the nasal-pharyngeal tract or to the skin.,Pulmonary Drug Delivery,Pharmaceutic

32、al Aerosols:Cromolyn Sodium Aerosol Trade Name:Intal Aerosol Mfg.:Fisons Use:Antiasthmatic;AntiallergicCromolyn sodium for inhalation usp:Trade name:Intal Use:Antiasthmatic,Pulmonary Drug Delivery,Epinephrine inhalation solution usp:1%Epinephrine aqueous solution use:BronchodilatorWARNING:Protect fr

33、om light.Do not use if brown in color or contains precipitate.Epinephrine inhalation aerosol usp:This preparation is a solution of epinephrine in propellants and alcohol.,Pulmonary Drug Delivery,Isoproterenol HCL inhalation aerosol usp:Trade name:Isuprel Mistometer aqueous solution of isoproterenol

34、HCL salt.It contains NaCl to achieve isotonicity.Strength:0.25,0.5,1%Use:Bronchodilator,Pulmonary Drug Delivery,Isoproterenol sulfate inhalation usp:Trade name:Norisordrine aerotrol contains 0.2%of the drug in metered aerosol.Amyl nitrite inhalant usp:Use:Vasodilator,Pulmonary Drug Delivery,Propylhe

35、xadrine inhalant usp:Use:AdrenergicMetaproterenol sulfate inhalation aerosol usp:Use:BronchodilatorTuaminoheptane inhalant usp:Use:Vasoconstrictor,Miscellaneous preparation,COLLODIONS:These are liquid preparations composed of pyroxylin dissolved in alcohol and ether,with or without added medicinal s

36、ubstances.Pyroxylin(soluble gun cotton)is obtained by the action of a mixture of nitric and sulfuric acids on cotton and consists of cellulose tetranitrate.,Miscellaneous preparation,Available commercially moistened with 30%alcohol.StorageHighly flammable;must be stored away from flame,well-closed c

37、ontainers,protect from light.Use:For external use only.Disadvantage:Inflexible in nature,Miscellaneous preparation,Flexible collodion:Prepared by adding 2%of camphor and 3%of castor oil to collodion.Salicylic acid collodion:10%solution of salicylic acid in flexible collodion.Use:Keratolytic(Remove c

38、orns)Marketed Preparations:Compound W(Whitehall),Miscellaneous preparation,Freezone(Whitehall)Direction of use:Apply one drop at a time onto the corn-allow time to dry-apply next drop.Caution:Salicylic acid can be irritating to normal,healthy skin.,Miscellaneous preparation,LINIMENTS:Alcoholic or ol

39、eaginous solutions or emulsions of various substances intended for external application to skin,generally with rubbing.,Miscellaneous preparation,Labels:1.External Use2.Shake WellStorage:store in a tight container,Miscellaneous preparation,GLYCEROGELATINS:Plastic masses intended for topical applicat

40、ion.Contains gelatin,glycerin,water,medicinal agents.Medicinal agents:Zinc oxide,salicylic acid,resorcinol,and other,Miscellaneous preparation,Application Procedure:Melted prior to application-cooled to only slightly above body temp.Applied to the affected area.Allowed to remain in place for periods

41、 up to 6 weeks or longer.,Miscellaneous preparation,Usual Concentration of drugs 10%Typical FormulationMedicinal Substance 100gGelatin 150gGlycerin 400gPurified Water 350g 1000g,Miscellaneous preparation,Zinc Gelatin:Firm plastic mass containing 10%zinc oxide in Glycerogelatin Base.Use:For the treat

42、ment of various ulcers.Make it soft on a water bath before application.,Miscellaneous preparation,PLASTERS:These are solid or semisolid adhesive masses spread upon a suitable backing material.Use:external application to a part of the body to provide prolong contact at that site.,Miscellaneous prepar

43、ation,Backing Materials Used:Paper,Cotton,Silk,PlasticType:Medicated:For localized or systemic effectNonmedicated:For mechanical support,Miscellaneous preparation,Commercially Available Plasters:Are used as back plasters,chest plasters,breast plasters,kidney plasters,corn plasters.,Miscellaneous pre

44、paration,Salicylic Acid Plaster:Concentration 10 to 40%For maximum result soak the corn in warm water for 15 to 30 minutes,prior to application of the plaster.Do Not Use For More Than 14 Days,Miscellaneous preparation,TAPES AND GAUZES:Adhesive Tape:Fabric and/or film evenly coated on one side with a

45、 pressure sensitive adhesive mixture.1.Sterile Tape2.Nonsterile Tape,Miscellaneous preparation,Absorbent Gauze:This is cotton or a mixture of cotton and rayon in the form of a cloth.Gauze Bandage:This is one continuous piece of absorbent gauze,tightly rolled in various widths and lengths and substan

46、tially free from loose threads.,Miscellaneous preparation,Adhesive Bandage:This is a compress of four layers of absorbent or other suitable material,affixed to a film of fabric coated with a pressure sensitive adhesive substance.-Sterile,Miscellaneous preparation,Petroleum Gauze:This is a absorbent

47、gauze saturated with white Petrolatum-Sterile Add white Petrolatum to dry sterile absorbent gauze 60 g Petrolatum to 20 g gauze,Miscellaneous preparation,Rubbing Alcohol:Contains about 70%of Ethyl Alcohol by volume.Use:Externally for bedridden patients.1.Germicide for instruments 2.Skin cleanser prior to injection,Miscellaneous preparation,Isopropyl Rubbing Alcohol:Contains about 70%by volume of Isopropyl AlcoholUse:Disinfecting the skin;Disinfecting needles and syringes.,Miscellaneous preparation,Hexachlorophene Liquid Cleanser:1.Bacteriostatic Cleansing Agent2.Staphylococci,