PHARMACEUTICAL AEROSOLS INHALANTS.pptx

AEROSOLS

1. AEROSOLS www.medacademy.org.in

2. 2 www.medacademy.org.in According to the present day usage , an aerosol or pressurized package is defined as “A system that depends on the power of a compressed or liquified gas to expel the contents from the container.” PHARMACEUTICAL AEROSOLS are pressurized dosage forms containing one or more active ingredients which upon actuation emit a fine dispersion of liquid and/or solid materials in a gaseous medium. Pharmaceutical aerosols are used for topical administrationfor the treatment of burns, minor cuts, infections and various dermatological preparation. DEFINITION

3. 3 www.medacademy.org.in Propellant Container Valve & actuator Product concentrate COMPONENTS OF AEROSOLS

4. 4 www.medacademy.org.in It is responsible for developing the power pressure with in the container and also expel the product when the valve is opened and in the atomization or foam production of the product. TYPES OF PROPELLANT For oral and inhalation eg. Fluorinated hydrocarbons such as Trichloromonofluoromethane (propellant 11) Dichlorodifluoromethane (propellant 12) Dichlorotetrafluoromethane (propellant 114) For Topical preparation: Hydrocarbons such as Propane Butane Isobutane Compound gases such as Nitrogen Carbon dioxide Nitrous oxide PROPELLANTS

5. 5 www.medacademy.org.in Numbering OF CFCs There are 3 digits 1 st digit represents-No. of carbon minus 1 2 nd digit represents- No. of hydrogen plus 1 3 rd digit represents- No. of fluorine atom DALTON’S LAW: The vapor pressure of a mixture of propellants can be calculated according to Dalton's law, which states that the total pressure in any system is equal to the sum of the individual or partial pressures of the various components. RAOULT’S LAW: Raoult's law, which regards lowering of the vapor pressure of a liquid by the addition of another substance, states that the depression of the vapor pressure of a solvent upon the addition of a solute is proportional to the mole fraction of solute molecules in the solution. PROPELLANTS

6. 6 www.medacademy.org.in They must be stand at pressure as high as 140 to 180 psig (pounds per sq. inch gauge) at 130 F. A. Metals 1. Tinplated steel (a) Side-seam (three pieces) (b) Two-piece or drawn (c) Tin free steel 2. Aluminium (a) Two-piece (b) One-piece (extruded or drawn) 3. Stainless steel B. Glass 1. Uncoated glass 2. Plastic coated glass CONTAINERS

7. 7 www.medacademy.org.in The present–day aerosol valve is multifunctional in that it is capable of being easily opened and closed and is capable of delivering the content in the desired form. FUNCTIONS: To deliver the drug in desired form. To give proper amount of medication. Types of valves - Continuous spray valve - Metering valves VALVES & ACTUATORS

8. 8 www.medacademy.org.in CONTINUOUS SPRAY VALVES An aerosol valve consists of many different parts and is assembled using high-speed production techniques. These valve assemblies consist of the following parts. VALVES & ACTUATORS COMPONENTS OF VALVE MATERIALS OF CONSTRUCTION Ferrule or mount cap Aluminium or brass Valve body or housing Nylon or Delrin Stem Nylon, Delrin, or Aluminium Gasket Buna N and Neoprene Spring Stainless steel Dip tube Polypropylene and polyethylene

9. 9 www.medacademy.org.in ACTUATOR To ensure that aerosol product is delivered in the proper and desired form, a specially designed button or actuator must be fitted to the valve stem. Different types of actuators Spray actuators Foam actuators Solid steam actuators Special actuators VALVES AND ACTUATORS

10. 10 www.medacademy.org.in SPRAY ACTUATORS: A spray type actuator can be used with pharmaceuticals intended for topical use, such as spray-on bandages, antiseptics, local anesthetics, and foot preparations. These actuators are capable of "mechanically" breaking a stream into fine particles by causing the stream to "swirl" through various channels built into the actuator. FOAM ACTUATORS: These actuators consist of relatively large orifices ranging from approximately 0.070 inch to 0.125 inch and greater. Used for semisolid products. SOLID STREAM ACTUATORS : The dispensing of such semisolid products as ointments generally requires these actuators. SPECIAL ACTUATORS: They are designed to deliver the medication to the appropriate site of action-throat, nose, eye, or vaginal tract. VALVES AND ACTUATORS

11. 11 www.medacademy.org.in Aerosol contains two essential components Product concentrate Propellant Product concentrate Product concentrate contains ingredients or mixture of active ingredients and other such as solvents, antioxidants and surfactants. Propellant May be single or blend of various propellants. Blends of propellant used in a pharmaceutical formulation to achieve desired solubility characteristics or various surfactants are mixed to give the proper HLB value for emulsion system. To give the desired vapor pressure, solubility & particle size. FORMULATION OF PHARMACEUTICAL AEROSOLS

12. 12 www.medacademy.org.in Depending on the type of aerosol system utilized, the pharmaceutical aerosol may be dispensed as a fine mist , wet spray, quick-breaking foam, stable foam, semisolid, or solid. The type of system selected depends on many factors , including Physical, chemical and pharmacologic properties of active ingredients. Site of application PARAMETERS CONSIDERATION

13. 13 www.medacademy.org.in Solution system Water based system Suspension or Dispersion systems Foam systems 1. Aqueous stable foams 2. Nonaqueous stable foams 3. Quick-breaking foams 4. Thermal foams Intranasal aerosols TYPES OF SYSTEM

14. 14 www.medacademy.org.in SOLUTION SYSTEM: This system is also referred to as a two-phase system and consists of a vapor and liquid phase. Aerosols intended for inhalation or for local activity in the respiratory system in the treatment of asthma may be formulated WATER BASED SYSTEM: This is three phase system which included propellant phase, water phase and vapor phase. Since propellant and water are not miscible, a three phase aerosol form. SUSPENSION SYSTEM: These systems have been developed primarily for use with oral inhalation aerosols. To decrease the rate of settling of the dispersed particles, various surfactants or suspending agents have been added to the systems. FORMULATION OF AEROSOLS

15. 15 www.medacademy.org.in FOAM SYSTEMS: Emulsion and foam aerosols consist of active ingredients, aqueous or nonaqueous vehicle, surfactant, and propellant, and are dispensed as a stable or quick-breaking foam, depending on the nature of the ingredients and the formulation. NONAQUEOUS STABLE FOAMS. Nonaqueous stable foams may be formulated through the use of various glycols such as polyethylene glycol. QUICK-BREAKING FOAMS. This type of system is especially applicable to topical medication, which can be applied to limited or to large areas without the use of a mechanical force to dispense the active ingredients. FORMULATION OF AEROSOLS

16. 16 www.medacademy.org.in THERMAL FOAMS : These systems would be advantageous in dispensing medicated foams in which the application of heat would be desirable. INTRANASAL AEROSOLS: Drug delivery systems intended for the deposition of medication into the nasal passageways has long been used as a most effective means of administering drugs intended to produce either a local or systemic effect. T he modes of administering intranasal preparations have been limited to nasal drops, nonpressurized nasal sprays (mists), inhalants, and intranasal gels (jellies), creams, and ointments. FORMULATION OF AEROSOLS

17. 17 www.medacademy.org.in Apparatus Pressure filling apparatus Cold filling apparatus Compressed gas filling apparatus MANUFACTURE OF AEROSOLS

18. 18 www.medacademy.org.in PRESSURE FILLING: Carried out at room temperature utilising pressure equipment. Useful for most pharmaceutical aerosols. Less danger of moisture contamination of the product. COLD FILLING Chilling the component (Propellant & Product) to temperature below 0 C. Aqueous solution cannot be filled by this process, since the water will turn to ice due to the low temperatures. COMPRESSED GAS FILLING Since the compressed gas are under high pressure it requires pressure reducing valve. MANUFACTURE OF AEROSOLS

19. 19 www.medacademy.org.in Propellants Valves, actuator and dip tubes Testing procedure Valve acceptance Containers Weight checking Leak testing Spray testing QUALITY CONTROL FOR PHARMACEUTICAL AEROSOLS

20. 20 www.medacademy.org.in PROPELLANT : Gas chromatography is used to determine the identity of the propellant, and when a blend of propellants is used, to determine the composition. VALVES,ACTUATORS AND DIP TUBES: The object of this test is to determine the magnitude of the valve delivery and the degree of uniformity between the individual valves as related to the acceptance of any given lot of metered aerosol valves . VALVE ACCEPTANCE: The test procedure applies to two categories of metered aerosol valves having the following limits. For valves delivering: 54 μL or less, the limits are ±15%. 55 to 200 μL , the limits are ±10%. CONTAINERS : Containers are sampled according to standard sampling procedures and in a manner similar to valves. QUALITY CONTROL OF AEROSOLS

21. 21 www.medacademy.org.in WEIGHT CHECKING: The same procedure is used to check the weight of the propellant that is being added. LEAK TESTING: A means of checking the crimping of the valve must be available to prevent defective containers due to leakage. SPRAY TESTING: Many pharmaceutical aerosols are 100% spray tested. QUALITY CONTROL OF AEROSOLS

22. 22 www.medacademy.org.in A. Flammability and combustibility Flash point Flame extension, including flashback B. Physiochemical characteristics Density Moisture content Identification of propellant(s) Concentrate-propellant ratio Vapor pressure C. Performance Spray pattern Aerosol valve discharge rate Dosage with metered valves Net contents Foam stability Particle size determination Leakage D. Biologic characteristics E. Therapeutic activity EVALUATION PARAMETERS OF AEROSOLS

23. FLAME PROJECTION This test indicates the effect of an aerosol formulation on the extension of an open flame. Product is sprayed for 4 sec. into flame. Depending on the nature of formulation, the flame is extended, and exact length being measured with a ruler. 23 www.medacademy.org.in EVALUATION PARAMETERS OF AEROSOLS

24. FLASH POINT Determined by using standard Tag Open Cup Apparatus. Step involves are  Aerosol product is chilled to temperature of - 25 F and transferred to the test apparatus. Temperature of test liquid increased slowly, and the temperature at which the vapors ignite is taken a flash point. VAPOR PRESSURE Determined by pressure gauge or a water bath, test gauges and special equipment. Variation in pressure indicates the presence of air in headspace. A can punctuating device is available for accurately measuring vapor pressure. 24 www.medacademy.org.in EVALUATION PARAMETERS OF AEROSOLS

25. DENSITY Determined by hydrometer or a pycnometer. MOISTURE CONTENT Method used -- Karl Fischer method and Gas Chromatography has also been used IDENTIFICATION OF PROPELLANTS Gas Chromatography I.R Spectrophotometry 25 www.medacademy.org.in EVALUATION PARAMETERS OF AEROSOLS

26. AEROSOL VALVE DISCHARGE RATE Determined by taking an aerosol of known weight and discharging the contents for given time using standard apparatus. By reweighing the container after time limit has expired, the change in weight per time dispensed is discharge rate, which can be expressed as gram per seconds. Net contents Weight method Filled full container, and dispensing the contents Foam stability Visual evaluation Time for a given mass to penetrate the foam The use of rotational viscometers 26 www.medacademy.org.in EVALUATION PARAMETERS OF AEROSOLS

27. SPRAY PATTERN Method is based on the impingement of spray on a piece of paper than has been treated with dye-talc mixture. Depending on the nature of aerosol an oil soluble or water –soluble dye is use. Particle size determination Cascade impactor: used for distribution and determination of particle size from 0.1 µm to 30µm. Light scatter decay method : Porush , Thiel and Young used light scattering method to determine particle size. As aerosols settle in turbulent condition , the change in light intensity of Tyndall beam is measured Sciarra and Cutie developed method for the evaluation of different actuators based on particle size distribution. 27 www.medacademy.org.in EVALUATION PARAMETERS OF AEROSOLS

28. BIOLOGIC TESTING: Biologic testing of aerosols should include a consideration of therapeutic efficacy and toxicity. Therapeutic activity: Various testing procedures are available to determine the therapeutic activity of aerosols. These tests are similar to existing tests for nonaerosols . Toxicity: Inhalation toxicity can be accomplished by exposing test animaals to vapours sprayed from an aerosol container. 28 www.medacademy.org.in EVALUATION PARAMETERS OF AEROSOLS

29. A dose can be removed with out contamination of materials. The medication can be delivered directly to the affected area in a desired form, such as spray, steam, quick breaking foam or stable foam. Irritation produced by the mechanical application of topical medication is reduced or eliminated. Ease of convenience of application. Application of medication in thin layer 29 www.medacademy.org.in ADVANTAGES OF AEROSOLS

30. Chlorofluorocarbon fuels cause ozone layer exhaustion Inflammability Toxicity Explosive Costly 30 www.medacademy.org.in DISADVANTAGES OF AEROSOLS

31. 1. Pharmaceutics: Drug Delivery and Targeting, By Yvonne Perrie,Thomas Rades , Pharmaceutical Press, second edition. 2. Introduction to the Pharmaceutical Sciences, By Nita K. Pandit. 3. Aulton's Pharmaceutics: The Design and Manufacture of Medicines, edited by Michael E. Aulton , Kevin Taylor. 4. Remington: Essentials of Pharmaceutics, By Linda Ed Felton. 5. Pharmaceutical Dosage Forms and Drug Delivery, Second Edition, CRC Press, Pharmacy Education Series, by Ram I. Mahato , Ajit S. Narang. 6. Essentials of Physical Pharmacy, by CVS Subramanyam, Vallabh Prakashan . 7. Biopharmaceutics& Pharmacokinetics, D. M. Brahmankar . 8. Modern Pharmaceutics, Gilbert S. Banker and Christopher Rhodes. 9. Essentials of Physical Chemistry, B.S.Bahl , G.D.Tuli , S. Chand ltd. 2000. 10. Martin’s Physical Pharmacy and Pharmaceutical Sciences, Patrick J.Sinko , Lippincott Williams & Wilkins, 2011 11. Textbook of Pharmaceutics, E.A. Rawlins, Ballière , Tindall, 1977 12. The Theory and Practice of Industrial Pharmacy Leon Lachman, Herbert A Lieberman,Joseph L Kanig , Varghese Publishing House, 1976 13. Martindale : The Complete Drug Reference: 36 th Ad 31 www.medacademy.org.in REFERENCES

32. Thank You www.medacademy.org.in “MAKING PROFESSIONALS, PROFESSIONALLY”