INHALATION AEROSOLS: INHALATION AEROSOLS Prepared by- Mitesh P. Sonawane. Under the Guidance of – Mrs. Narkhede M.G.V.S Pharmacy College, Panchavati,Nashik Definition-: Definition- Pharmaceutical aerosols are products that are packed under the pressure and contain therapeutically active ingredient. That are release upon actuation of appropriate valve system. Advantages-: Advantages- Aerosol doses are generally smaller than systemic doses. Onset of effect with inhaled drugs is faster than with oral dosing. Drug is delivered directly to the lungs, with minimal systemic exposure. Systemic side effects are less frequent and severe with inhalation when compared to use of aerosol devices by patients and systemic delivery. Inhaled drug therapy is less painful than the injection and is relatively comfortable. Disadvantages: Disadvantages Lung deposition is a relatively low fraction of the total dose. A number of variables (correct breathing than with oral dosing. pattern, use of device) can affect lung deposition and dose reproducibility. The difficulty of coordinating hand action minimal systemic exposure. and inhalation with the pMDIs reduces effectiveness. The lack of knowledge of correct or optimal severe with inhalation when compared to use of aerosol devices by patients and systemic delivery. clinicians decreases effectiveness. The number and variability of device types confuses patients and clinicians. The lack of standardized technical information on inhalers for clinicians reduces effectiveness. Components of aerosol system: Components of aerosol system Propellant Container Valve assembly Drug concentrate Propellant: Propellant Propellant produces sufficient vapour pressure in the containtaer,so that medicament is expelled when valve is actuated. It may also act as solvent of drug. Generally mixture of propellant is used to get desired vapour pressure and solvent properties Ideal characteristic of Propellant: Ideal characteristic of Propellant Economical, Non-toxic Non-Irritant Odourless Physically and chemically stable Should dissolve wide range of medicament Compatible with container, valve system and drug Produces sufficient vapour pressure. Nonflammable and enviorment friendly. Slide 8: Vapor pressure of mixture of propellants is calculated by Doltan’s low which states that total Pressure in any system is equal to the sum of individual or partial pressure of various compounds Raoult’s low regards lowering of the vapor pressure of a liquid by the addition of another substance, States that the dispersion of the vapor pressure of solvent upon the addition of solute is proportion to the mole fraction of solute molecules in solution. The relationship can be shown mathematically : na pa = ------------ p A o = N A p A o ----------(1) na + nb Where, pa = partial vaopr pressure of propellant A, pAo = vaopr pressure of pure propellant A na = mole of propellant A, nb = mole of propellant B NA = mole fraction of component A Slide 9: Containers They must be stand at pressure as high as 140 to 180 psig (pounds per sq. inch gauge) at 130 0 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 Slide 10: Valves To delivered the drug in desired form. To give proper amount of medication. Not differ from valve to valve of medication in pharmaceutical preparation. Types - Continuous spray valve - High speed production technique. - Metering valves Dispersing of potent medication at proper dispersion/ spray approximately 50 to 150 mg ±10 % of liquid materials at one time use of same valve. Slide 11: Valve components Ferrule or mount cap Valve body or housing Stem Gasket Spring Dip tube Slide 12: Actuator To ensure that aerosol product is delivered in the proper and desired form. Different types of actuators Spray actuators Foam actuators Solid steam actuators Special actuators Classification: Classification Types of aerosol formulation: Types of aerosol formulation Small-volume Nebulizer: The SVN is an aerosol generator that converts liquid drug solutions or suspensions into aerosol and is powered by compressed air, oxygen, a compressor, or an electrically powered device. Slide 17: Pressurized Metered-dose Inhaler: The pMDI is a small, portable self-contained drug device combination that dispenses multiple doses by a metered value. Because of high medication loss in the oropharynx and hand-held coordination difficulty with pMDIs, holding chambers and spacers are often used as ancillary devices with the pMDI. Dry-powder Inhaler : The DPI is an aerosol device that delivers drug in a powdered form, typically with a breath-actuated dosing system. Pressurized Metered-dose Inhaler: : Pressurized Metered-dose Inhaler: The pMDI was designed and developed as a drug and device combination that delivers precise doses of specific drug formulations. Unlike nebulizers, drug preparation and handling is not required with pMDIs, and the internal components of pMDIs are difficult to contaminate. There are two major types of pMDIs: conventional pMDIs and breath-actuated pMDIs. Advantages of pMDIs: : Advantages of pMDIs: Portable, light, and compact Multiple dose convenience Short treatment time Reproducible emitted doses No drug preparation required Difficult to contaminate Disadvantages of pMDIs:: Disadvantages of pMDIs: Hand-breath coordination required Patient activation, proper inhalation pattern, and breath-hold required Fixed drug concentrations and doses High oropharyngeal deposition Difficult to determine the dose remaining in the canister without dose counter Components of pMDIs: : Components of pMDIs: Canister : Inert, able to withstand high internal pressures and utilize a coating to prevent drug adherence. Propellants : Liquefied compressed gases in which the drug is dissolved or suspended Drug Formulary : Particulate suspensions or solutions in the presence of surfactants or alcohol that allocate the drug dose and the specific particle size Slide 22: Metering Valve : Most critical component that is crimped onto the container and is responsible for metering a reproducible volume or dose Elastomeric valves for sealing and preventing drug loss or leakage Actuator : Frequently referred to as the “boot,” partially responsible for particle size based on the length and diameter of the nozzle for the various pMDIs (Each boot is unique to a specific pMDI/drug.) Slide 23: Dose Counter : This component provides a visual tracking of the number of doses remaining in the pMDI Figure . Standard components of pMDI Dry powder inhaler:: Dry powder inhaler: Dry-powder inhalers (DPIs) are portable, inspiratory flow-driven inhalers that are used to administer dry-powder formulations to the lungs. DPIs do not contain propellant and are breath-actuated. They have been developed to overcome the difficulties of using metered-dose inhalers and are often prescribed with the hope of providing the patient with an overall more user-friendly and more predictable therapy. Advantages: Advantages Small and portable Built-in dose counter Propellant free Breath-actuated Short preparation and administration time Disadvantages: Disadvantages Dependence on patient’s inspiratory flow Patient less aware of delivered dose Relatively high oropharyngeal impaction Limited range of drugs Easy for patient to confuse directions for use with other devices Types of DPIs: Types of DPIs DPIs can be classified into three categories based on the design of their dose containers, i.e., single-dose DPIs , Eg . Aerolizer ® is used for the delivery of formoterol multiple unit-dose DPIs , Eg . Diskhaler ® (GlaxoSmithKline) for delivery of zanamivir multiple-dose DPIs , Eg . Twisthaler ® is a multi-dose DPI used to deliver mometasone furoate . DPI design: DPI design (A) AerolizerTM , (B) EasyhalerTM , (C) TurbohalerTM , (D) DiskhalerTM , (E) NovolizerTM , (F) RotahalerTM ,(G) ClickhalerTM , (H) MAGhalerTM , (I) SpinhalerTM , (J) HandihalerTM Filling of aerosols: Filling of aerosols Pressure filling Filling is done at RT. Valve is placed on the container and sealed, air is evacuated from the container through the valve stem and then gas propellant is forced through stem. Cold filling Filling is done at -35 0C to -40 0C. Not suitable for aqueous products. Leakage test: 54.4 0C Evaluation: Evaluation » 1.Flash point: Apparatus : Open Cup Tag Apparatus Test liquids temp. is allowed to increase slowly & temp. at which vapors Ignite is called as Flash Point . » 2.Flame Projection: Product is sprayed for 4 sec onto flame & exact length is measured with ruler. Slide 32: 3. Physicochemical characteristics 1. Vapor Pressure » Can Puncturing Device. 2. Density » Hydrometer, » Pycnometer. 3. Moisture » Karl Fisher Method, » Gas Chromatography. 4. Identification » Gas Chromatography, » IR Spectroscopy. 4.Performance: : 4.Performance : 1.Aerosol valve discharge rate : Aerosol product of known weight is discharged for specific time. By reweighing the container, the change in the wt. per time dispensed is the Discharge rate in gm/sec. 2. Spray pattern : The method is based on the impingement of spray on piece of paper that has treated with Dye-Talc mixture. 5. Dosage with metered valves :: 5. Dosage with metered valves : Reproducibility of dosage determined by: »Assay »Accurate weighing of filled container followed by dispensing several dosage. containers again reweighed & diff. in wt. divided by no. of dosage dispensed gives average dose. 6. Net Contents : Tared cans placed on filling lines are reweighed & then difference in wt. is equal to net content. In Destructive method : opening the container & removing as much of product possible. Slide 35: 7.Partical Size Determination : Methods : » Cascade Impactor , » Light Scattering Decay. a). Cascade Impactor : Principle : Stream of particle projected through a series of nozzle & glass slides at high velocity, larger particle are impacted on low velocity stage , & smaller on higher velocity stage. Slide 36: b). Light Scattering Decay : Principal : As aerosol settles under turbulent condition, the changes in the light of a Tyndall beam is measured. 8. Biological testing: 1.Therapeutic Activity : » For Inhalation Aerosols : is depends on the particle size. » For Topical Aerosols : is applied to test areas & adsorption of therapeutic ingredient is determined. Slide 37: 2.Toxicity : » For Inhalation Aerosols : exposing test animals to vapor sprayed from Aerosol container. » For Topical Aerosols : Irritation & Chilling effects are determined. References:: References: “The Theory & Practice Of Industrial Pharmacy” by Leon Lachman , H.A.Liberman , Joseph Kanig , 3 rd Edition, Varghese Pub., page no. 613-618. Remington’s “The Science & Practice Of Pharmacy” 3 rd Edition, Volume-I, page no.1014-1015. Dry powder inhaler From Wikipedia, the free encyclopedia Dry Powder Inhalers - An Overview M. Alagusundaram *, N. Deepthi , S. Ramkanth , S. Angalaparameswari , T.S. Mohamed Saleem , K. Gnanaprakash , V. S. Thiruvengadarajan , C. Madhusudhana Chetty Annamacharya College of Pharmacy, Rajampet , Kadapa -District, Andhrapradesh , India Slide 39: Thank You....!