yr Pharmaceutical Aerosols 22 pintessstecl isused when the st container must be mite. The tain limitation « at be of these cont, chemically resistant to the product nerd Hive ainers is their high cost. atic containers : rr Se Antec access because of their inherent permeability mjemns 1211 8 side the containe ? a peu ve efficacy at the product Fakes th Io, some drug-plastic interactions pane 0 Ty of conor US wage . = Prosaure limitations Of aeronot containers 7a iar material Maximum pressure (psig), Fr pated ot00 180 Temperature (7) meaied ats <18 7 red ast <25 n ur 180 ‘20 aiess $1001 180 190 paste = 7 uve ASSEMBLY vty oitectiveness of a pharmaceutical aera Ws pnation of product concentrate formulati vijve mechanism is the part of the sol depends on achieving th ion, container and valve assembly. fre Product package through whi ver are emitted, The valve must withstand the press eee ieg ets of the id the pressure required by the product ventrate and the container, be corrosive produc tye emitted product concentrate esistant and must contribute to the form The primary purpose of the valve is tor om the container. But the valve must also be multifunctional . seit material (metered valves), be capable ‘of delivering te paduet eeearmtate nthe desired form, and be easy to tum on and off. Among the materials used in the manufacture of the various valve parts are plastic, rubber, aluminum, and stainless steel (Fig. 10.4). the basic parts of a valve assembly are: 1 Actuator: The actuator is the button which the user presses to activate the valve assembly and provides an easy mechanism of turning the valve on and off. In some actuators, mechanical breakup devices are also included. It is the combination of the type and quantity of propellant used and the actuator design and dimensions that determine the physical form of the emitted product concentrate. 2.Stem: The stem supports the actuator and delivers the formulation in the proper form to the chamber of the actuator. }. Gasket: The gasket, placed snugly with the stem, serves to prevent leakage of the formulation of the valve is in the closed position. 4 Spring: The spring holds the gasket in place and also is the mechanism by which the actuator retracts when pressure is released thereby returning the valve to the closed position. 5. Mounting cup: The mounting cup which is attached to the aerosol container serves tohold the valve in place. Because the undersigned of the mounting cup is exposed to the formulation, it must receive the same consideration as the inner part of the regulate the flow of product concentrate Scanned with CamScanneroumutanwe Pharmacy: TREOTY min ree m22| a Actumor oon Sa.. ves =e —— _ — ove o s asic parts of valve assembly +o meeting criteria of compatibility. If necessary, it may by to prevent an undesired interaction. container with respect rectly below the mounting cup se direct Up serves as ith an inert material coated aeaied The housing locate’ mi Sore weer the dip tube and the stem andl actuetor With the stem, its orifice helps tg rc pipe ate and the form in which the product is emitted, i tube which extends from the housing down into the product @ container to the valve. The ing the from th vipentrate serves to bring the formulation 0 t concentra ine product and its intended delivery to rate dictate the inner dimensions of the dip tube and housing for a particular product. Spray valves are used 10 obtain fine to coarse wel sprays, Depending on the fon ttion and the design of the valve and actuator, the particle size of the emuteg sae pe varied. The spray is produced as an aerosol solution passes througha i enall orifices which open into chambers that allow the product concentrate to expand into the proper particle size. Vapor tap valves are used with powder aerosols, waler based aerosols, aerosols containing suspended materials, and other agents that would tend to clog a standard valve. This valve is basically a standard valve except that a small hole has been placed propellant to be emitted along with the into the valve housing. This allows vaporized centrate and produces a spray with greater dispersion. These valves are queous and hydroalcohalic product concentrates and hydrocarbon determine the deli 7. Dip tube: The dip spray series ol product coni used with a propellants. Foam valves have only one orifice that leads to a single expansion chamber. The expansion chamber also serves as the delivery nozzle or applicator. The chamber is the appropriate volume to allow the product concentrate to expand into a ball of foam Scanned with CamScanner— Mharmacenea peroses 29 all be wenitied ae so ‘lo het the at (MDD valves (metering va ate Matera! wales are une fo alonal inna acutally liver eaten wat ly deliver any vive pa kay I allow for th an te eae Cane . in yp aerrmct Wrslom serial ne the valve hein general va ver ty bn pate Wy Heth ae the the const lon of the valves. Sime annie this problem, main ip oy hand tt fa hal 1 the chamber " Valves have been fit ened of Manutoctuting melt manufact tons al il prscens fresnel peo re ‘anil process: The cold fill process takes advantage o resents will Uguety when cooled, and the pressure fil proces toes toa {rome ingredients will liquety when placed under presses pee the cold fil procens, both the product concentrate and the propellant must be wal t temperatures between “WFC and Gi" whee Ivremain hquehed ‘coma. syle may be a minted dry ke teleige concentrate is quantitatively added te the eally sn cuntadner annd then the liquefied ysis added “The heavy will generally displace the Ive assembly in ise of the property that sume Japon of the «ld cr. When tilling, the container and crimped inte pla comiuner is then passed through a water bath of about 58°C to check for leaks or ssuitin in the container, Aqueous solutions cannot be filled by this procens since the water will turn to ice in telow temperatures, For nonaqueous systems, some moisture usually appears in the sal product due to the condens nospheric maisture with old stants (Powehatt 10.1) ‘rowan fil process: Prowure filling is carried out ewsentially at room temperature prac! concentrate is placed in the container, the valve asembly is inserted and ‘imped into place, and then the liquefied gas, under p iv added through the she The entrapped air in the package might be ignored if it does not interfere with, Scanned with CamScannerFormntive Pharmacy: Theory and Practical Flowehart 10.1; Methor! of manutactura by Cold I mato Coot the product conenntrata to 40°F Ft into the cooled container J] Cool the propemant J ‘ata propahant ot pret concartvate | actuated prion to filling ¢ valve tn tested for Proper 17.8 by propellant prior to consumer wa the wets M has the advantage thar, ee gannture contamination of the prod! andl ase less prapetiyny ob proves (Howsehart 10.2) Mn ge Aenwols are used to deliver active drugs to the pulmonary ANEW AY, the passages or the: oral cavity. They are also tused toadminister drugs topical Rak Shits such the vagina and rectum, Pulmonary, nasal, and onal gq! ain is intended to achieve either local or systemic therapeutic effect, while topic a, an retal administration ts only intended for local effect. Inhalation therypy 12% delivery to the pulmonary airways and nasal passages) was once accomplnheg dry nebulizers or atomizers that were cumbersome to use and restricted to instin tng home use, The development of the metered dose inhaler in the mid yep. er the convenience of portability with the accuracy of dosing, Provide Successful inhalation therapy requires that the formulation emit droplets or that are the optimum size. Large particles (about 20 jum) deposit in the b, Part, mouth and throat and are eventually swallowed rather than inhaled, Parhese 1 to 10 wm range will reach the bronchioles, Very small particles (0.6 ym) poxnen the alveolar sacs but have limited retention since a large fraction of the ae exhaled in the breath, The most therapeutically effective particle size range apron be between 3 and 6 jim, Therefore, its important that the aerosol syeaag PD” ‘most of its particles between approximately 1 and 10 yim. Produce MDIs are the most commonly used product for inhalation therapy and i of the most difficult dosage forms to administer properly. One of the Trost oan maneuvers during administration is to coordinate the actuation of the aerosol was the patient's inspiration. The mouthpiece adapter on the acrosol Package has been the statutity of the pronfuet, oF It may be Atter the filling operation ts complete, the vray teatinyg alse Fic the dip ibe op a nynst pharmaceutical a filling used f Flowchart 10.2: Method of manufacture by pressure fill method Fill the container wih product concenirata Place tne value in ts position by compression’ Now iireduce aie Scanned with CamScanner225 Pharmaceutical Aerosols i receive the ce the mid 1970s in an attempt to help patients fified sine yy mod vctly, Larger adapters coordination is not Performed correctly hareer a before cell igo when this cers) permit the Propellant to completely evap ie belore Sn hibe spacer This resultsin a reduced partic ize and velocity. , eaches the pa i into the improves the depth to. Which the drug will Penetration ipa ice ver velocity decteases the amount of hae the Toy * and drug that will impact on ne The biggest disadvantages of these larger adapters are the cost, info the throat and inconvenience heir sive. ty toclean, a me we a gol TE ans to use because of th Is deliver the drug directly to the nasal Nasal aerosols de treat nasal conge. a aes contain steroids used to treat nasal ¢ 2 ' y aerosols. dwith hay fever, lergies, and thinitis. Such Products use steroids such . Ot one dipropionate, triamcinolone acetonide, dexamethasone sodium x become! rid budestnile Attosols used to delives rugs to the oral cavil ir the prodt Sublingually. One suck Ereduct is a sublingual ni xaitanon that sprayeg under the tongue any delivers 0.4 me oPnit jolla on Mipleal aerosol formulations foeides frst ad Preparations, ¢ ses that are larger and more Fave the active dies '¢ most common stion, sneezing, and running Toglycerin oglycerin per » antiseptics, 'erosol deliver els: Topical aerosols "Wet spray, a Stream of liquid, o¢ an sintment like product. Vaginal and rectal foams are available ' contain eg BENS, cont tives, and untrinflammation agents, Se Products Fe Packaged ' containers, 4 t have an plication device which ig filled with foa spp i mm When the val S actuated and then Sie placed in the vagina st "Um and the foam 'sinstilled with th evice plunger INUATION TEST AND, QUALITY CONTROL OF AEROSOLS fraluation Tests Marmaceutical aero so} can be evatua it it paral Performance Sval Te LY testing faramabitity Cmbustibility, antmany tests arg eecessary to engi prove pee ma nd aes during the use and Storage evalua ero oem ne eee and safety Flammability ang combustibility Meno Inclades Nowing ests |. Flash point 8 Projection & hysiochemical characteristics 1. Vapour Pressure 2 “Nsity and wei, it 3 Moisture content Meetiica on of Propellants 6; “Tetformance 2 8080 vate di 2 Spray Pattern “*hrge rate ~ Scanned with CawScannerFormulative Pharmacy: Theory and Practical 26 — 4. Dosage with metered valves 4, Net contents 5, Foam stability 6 Particle size determination Leakage test rgzical testing, 1. Therapeutic activity 2 Toxicity studies 3, Extractable substances A Flammability ond Combustibillty “standard tag open CaP apparatus” is used for determi in Fash paint “St ton int (Fg, 10:5), Fo tis the formula ion chilled to tern ation ¢ Ponwterned to the festapparates, The temperature of test sample liguiel of ast tranatorm perature at which the vapors of propellant ignite i guid increase ye an tN ated for flammable component, which In case of topical past pond! s ical hyde Pon Oca mn propellants Flame projection i. Flame test in open flame (Fig. 10.)- ii anresol product is sprayed ford sec into open flame. iii, Depending on the nature and type of formulation, the f i Terpah and exact length was measured with rule. abe tame ws extended to samy dicates the effect of an aerosol formulation on the extension an 2. Physicochemical Characteristics Vapour pressure: Vapour pressure is determined b y pressure through use of a water bath, test gauges and other special cquipmen or el he presence of air in headscape. Variation in Pree past ape. For accurate measurement of va aces ig device is used. Pour pressure pressure indicates t presence of air in the headsc; aerosol container can punctuatin| Fig. 10.8: Flash pol Point tag open cap apparatus Fig. 10.6: Flame projection test appere™* Scanned with CamScanneracitv Of Aerosol eye ay 108) ae a coe PREPARATION, In which a proses whieh under preecant T is hope sample is addled thre IN OF the tube Ty hydromet setae COMEEMES KOU Fischer wdcntifieation of pro, Pellants: oe wsst ROP dent mn « SHOMPOHEAL AN a Bench aH plimetor ts used °POION of the VN pH range of 9 to 105 is optim, A pll range of 4.5 10.8.5 4g PML for 1S optimal fo « pli less than 8 problematic for unlined container, » PHican drift over product lifeg nie sel e uscosity: Thi Te Te ANY types of te, . 7 uluct viscosity. They all tend tote it!Pment and \ethod: 4 salut viscosity, They O involve either rors s for determinin, “S10 soy, toes Variations in viscosity can have dramatic of Non or capillary exes 1 Time and effort spent compounding and filling SM the following. CO, absorption, in. a Spray pattern, Claboratay Foam stability, ‘ariation \ Spray out appearance, “dicates the v. Low temperature usabil > Read at bottom of meniscus reading 225 Fig. 10.8: The pycnomete Fig. 10.7; The hydrometer ipparatus Scanned with CamScanner