ThePreferredMethodofGasPermeabilityTestforDrugPackagingMaterials

　　The Preferred Method of Gas Permeability Test for Drug Packaging Materials-Differential Pressure MethodAbstract: based on YBB00082003 Test Methods of Gas Permeability, this article presents a detailed introductionto the methods of gas permeability test. It also deals with the latest developments of each method as well as howspecific drug packaging material standard influence the application of permeability test methods.Key words: drug, drug packaging materials, and oxygen permeabilityThe application of packaging materials with excellent barrier property can efficiently prolong qualityguarantee period, expand storage environment of products, thus providing more conveniences to transportationand storage. For the above-mentioned reason, the application of barrier materials witnessed a very rapiddevelopment. Test methods of gas permeability can be divided into differential-pressure method andequal-pressure method. The influence of different test methods on test data cannot be completely eliminated.Because the methods of barrier property test are not well understood, current drug packaging enterprises do notpay much attention during the purchasing of permeability testers. To establish a uniform test method for barrierproperty test of domestic drug packaging materials and to improve the comparability of test data, the State Foodand Drug Administration of the People’s Republic of China issued YBB00082003 Test methods of GasPermeability, which becomes the directory in selecting gas permeability testers.YBB00082003 Gas Permeance Measurement provides two methods: differential pressure method andcoulometric method, which will be dealt with in detail below.1.Differential Pressure MethodDifferential pressure method is formulated in accordance with ISO 15105-1, ISO 2556, GB 1038-2000. Indifferential pressure method, higher-pressure chamber and low-pressure chamber are separated by drugpackaging film or sheets. There is one pressure gauge in each chamber. The high-pressure chamber is filled withtest gas of about 0.1MPa and the low-pressure chamber has known volume. Vacuumize the low chamber toabout zero after the sealing of test finishes and then measure the pressure increment of low-pressure chamberwith pressure gauge. In this way, gas permeance- function of time, from high-pressure chamber into low-pressurechamber can be determined. However, the initial period of transmission rate with time should be excluded. Whenthe pressure variation rate of low-pressure chamber becomes stable, that is to say the gas permeance becomesstable, users can calculate gas permeance and gas permeability coefficient according to the formula offered inthe standard. The unit is cm3/m2·24h·0.1Mpa. It should be specially noted that in the initial period of test, thewhole permeable chamber should be vacuumized to below 27kPa with additional continuous outgassing.Differential pressure method can also test gas permeability coefficient to materials, diffusion coefficient of gaseswithin materials and solubility coefficient of materials to gases. It can also be used to test common inorganicgases such as oxygen gas, nitrogen gas, carbon dioxide and air.In the draft of YBB00082003, it is stated that the differential pressure method is formulated referring to GB/T1038-2000 test method of gas permeance for plastic films and foils-differential pressure method. After comparingthe methods in these two standards we can see that the requirements are basically the same while the content ofGB/T 1038-2000 is more complete than that of YBB00082003. Therefore, GB/T 1038-2000 can completely meetwhat required in the first method of YBB00082003. note that comparing with current international test standardsof film permeability test with differential pressure method such as ASTM D1434、ISO 15105-1、ISO 2556：2001,Labthink Instruments CO.,LTD.144Wuyingshan Road, Jinan, ChinaTel: +86-531-85811021 85864214Fax: +86-531-85812140E-mail: trade@labthink.cnGB/T 1038-2000 is less complete in terms of detailed operation rules. But its demand on various parametersduring test is uniform with that of these international standards. For instance, it is specified in ASTM D 1434-82（2003）that the vacuum degree of low-pressure side of test chamber should be lower than 26Pa, while that isrequired to be no high than 27 Pa in standards ISO 2556:2001and GB/T 1038-2000.2. Coulometric MethodYYB00082003 formulate the coulometric method (the second method in the standard) While reserving thedifferential pressure method.The coulometric method, or the sensor method, belongs to equal pressure test method. In this method, thepermeable chamber is divided into two independent airflow systems by drug packaging film or sheet, with oneside being the flowing testing gas (pure oxygen or mixed gas of oxygen) and the other side being the flowing drynitrogen gas. The pressure of the two sides is equal but oxygen partial pressure is different. Under the function ofoxygen concentration difference, oxygen transmits through the film and is diverted into the sensor by nitrogencarrier gas. Oxygen permeability of the package can be calculated with the oxygen quantity in nitrogen carriergas is accurately measured by the sensor. The unit of oxygen permeance, tested in coulometric method withoutcalibration, is cm3/m2·d. Instruments of coulometric method should be calibrated with standard film before test.Calibration coefficient of instrument should also be determined. For differential pressure method and equalpressure method, the test principle and test conditions are different. The units of their results are also different.Therefore, there is no comparability of the non-calibrated data obtained from the two methods. But thecomparison becomes possible after calibrating the instrument with standard film. In addition, the data ofcoulometric method can be traced back to differential pressure method, which is clearly specified in ASTMD3985-05：“Limited statistical data on correlations with Test Method D1434 methods are available; however, theoxygen transmission rate of a standard reference material as determined manometrically by NIST, is in goodagreement with the values obtained in the coulometric interlaboratory test using material from the samemanufacturing lot.”。Among it, ASTM D 1434 is the test standard of differential pressure method.Because the sensor used belongs to the consumptive type, corrected factor of the instrument is not alwaysvalid and needs to be periodically calibrated as required. the sensor must be changed when it deteriorates to acertain extend. At the same time, the consumption of oxygen gas and nitrogen gas during test is rather big. Thustest cost of this method is much higher than that of the differential pressure method.3.The Application of Test MethodsBased on specific executive standard of drug packaging materials, we will discuss the detailed application ofthe above-mentioned two methods:two methods:two methods:Table 1: gas permeability measurement of drug packing materialsYBB00082003Number ofstandardName of standardThe firstmethoddifferentialpressuremethodThe secondmethodcoulometricmethodYBB00132002General rules on laminated film and bag for drugpackaging√1 ×YBB00172002Laminated film and bag ofpolyester/aluminum/polyethylene for drugpackaging√1 ×YBB00182002Laminated film and bag of polyester/ low densitypolyethylene for drug packaging√1 ×YBB00192002Laminated film and bag BOPP/ low densitypolyethylene for drug packaging√1 ×YBB00242002Laminated sheet of polyamide/aluminum/pdythenefilm for cold forging moulded drug√1 ×YBB00342002 General rules on multi-layer co-extrusion √1，2 ×YBB00182004Laminated hard sheet of aluminum / pdythene forcold forging moulded solid drug√ √YBB00192004Laminated film and bag of BOPP/ Vacuumaluminum coated casting polypropylene for drugpackaging√ ×YBB00202004Laminated film and bag of cellophanepaper/aluminum/ polypropylene for drug packaging√ ×YBB00072005 Low density polyethylene film and bag for drug use √ ×YBB00102005 three-layer co-extrusion film（Ⅰ）,bag for transfusion √2 ×YBB00112005 five-layer co-extrusion film（Ⅰ）,bag for transfusion √2 ×YBB00202005Polypropylene/polyethylene/polyvinylidene chloridefor cold forging moulded solid drug√1 ×YBB00212005 Polypropylene hard sheet for solid drug √1 ×YBB00222005Laminated hard sheet ofpolypropylene/polyvinylidene chloride for solid drug√1 ×YBB00232005Laminated hard sheet of polypropylene/low densitypolyethylene for solid drug√1 ×YBB00252005Laminated flexible ointment tube of drugpolyethylene/aluminum/ polyethylene√ √Note: 1. if YBB00082003 has not been formulated at the time when current standard is being formulated or whenthe original standard of this modified standard is being formulated, the standard GB/T 1038-2000 wouldbe executed.2. oxygen permeance and nitrogen gas permeance of materials should be tested.From table 1 we can see that almost all the gas permeability tests of drug packaging materials are based ondifferential pressure method except. The coulometric method is applicable for gas permeability test of only twomaterials as the alternative method. Therefore, permeability testers differential pressure method can completelymeet the requirements of barrier property test. However, currently speaking, the coulometric method is unable tosatisfy the test requirements of most of the materials.4.ConclusionThe standard of gas permeability test for drug packaging materials is in accordance with international testmethods. Moreover, new test methods based on new industry characteristics of drug packaging industry areproposed. However, we can see from the above-mentioned analysis that although differential-pressure methodcan completely meet test requirements of drug packaging materials, the application of coulometric method israther narrow. Therefore, selecting gas permeability testers of differential pressure method can better meet therequirements of drug packaging test standards. It can also efficiently avoid the possible influence resulting fromthe adopting of different test methods, thus reducing test and improving productivity.