á671ñCONTAINERS—PERMEATION
The tests that follow are provided to determine the moisture permeability of containers utilized for drugs being dispensed on prescription.The section Multiple-Unit Containers for Capsules and Tabletsapplies to multiple-unit containers (see Preservation,Packaging,Storage,and Labelingunder General Notices and Requirements).The section Single-Unit Containers and Unit-Dose Containers for Capsules and Tabletsapplies to single-unit and unit-dose containers (see Single-Unit Containers and Unit-Dose Containers for Nonsterile Solid and Liquid Dosage Formsunder Containers á661ñ).As used herein,the term “container”refers to the entire system comprising,usually,the container itself,the liner (if used),the closure in the case of multiple-unit containers,and the lidding and blister in the case of single-unit and unit-dose containers.
Where the manufacturer's unopened multiple-unit,single-unit,or unit-dose packages are used for dispensing the drug,such containers are exempt from the requirements of this test.
MULTIPLE-UNIT CONTAINERS FOR CAPSULES AND TABLETS
Desiccant—
Place a quantity of 4-to 8-mesh,anhydrous calcium chloride1in a shallow container,taking care to exclude any fine powder,then dry at 110
for 1hour,and cool in a desiccator.
for 1hour,and cool in a desiccator.
Procedure—
Select 12containers of a uniform size and type,clean the sealing surfaces with a lint-free cloth,and close and open each container 30times.Apply the closure firmly and uniformly each time the container is closed.Close screw-capped containers with a torque that is within the range of tightness specified in the accompanying table.Add Desiccantto 10of the containers,designated test containers,filling each to within 13mm of the closure if the container volume is 20mLor more,or filling each to two-thirds of capacity if the container volume is less than 20mL.If the interior of the container is more than 63mm in depth,an inert filler or spacer may be placed in the bottom to minimize the total weight of the container and Desiccant;the layer of Desiccantin such a container shall be not less than 5cm in depth.Close each immediately after adding Desiccant,applying the torque designated in the accompanying table when closing screw-capped containers.To each of the remaining 2containers,designated controls,add a sufficient number of glass beads to attain a weight approximately equal to that of each of the test containers,and close,applying the torque designated in the accompanying table when closing screw-capped containers.Record the weight of the individual containers so prepared to the nearest 0.1mg if the container volume is less than 20mL;to the nearest mg if the container volume is 20mLor more but less than 200mL;or to the nearest centigram (10mg)if the container volume is 200mLor more;and store at 75±3%relative humidity and a temperature of 23±2.[NOTE—Asaturated system of 35g of sodium chloride with each 100mLof water placed in the bottom of a desiccator maintains the specified humidity.Other methods may be employed to maintain these conditions.]After 336±1hours (14days),record the weight of the individual containers in the same manner.Completely fill 5empty containers of the same size and type as the containers under test with water or a noncompressible,free-flowing solid such as well-tamped fine glass beads,to the level indicated by the closure surface when in place.Transfer the contents of each to a graduated cylinder,and determine the average container volume,in mL.Calculate the rate of moisture permeability,in mg per day per L,by the formula:
.[NOTE—Asaturated system of 35g of sodium chloride with each 100mLof water placed in the bottom of a desiccator maintains the specified humidity.Other methods may be employed to maintain these conditions.]After 336±1hours (14days),record the weight of the individual containers in the same manner.Completely fill 5empty containers of the same size and type as the containers under test with water or a noncompressible,free-flowing solid such as well-tamped fine glass beads,to the level indicated by the closure surface when in place.Transfer the contents of each to a graduated cylinder,and determine the average container volume,in mL.Calculate the rate of moisture permeability,in mg per day per L,by the formula:
(1000/14V)[(TF–TI)–(CF–CI)],
in which Vis the volume,in mL,of the container,(TF–TI)is the difference,in mg,between the final and initial weights of each test container,and (CF–CI)is the difference,in mg,between the average final and average initial weights of the 2controls.For containers used for drugs being dispensed on prescription,the containers so tested are tight containersif not more than one of the 10test containersexceeds 100mg per day per Lin moisture permeability,and none exceeds 200mg per day per L.
For containers used for drugs being dispensed on prescription,the containers are well-closed containersif not more than one of the 10test containersexceeds 2000mg per day per Lin moisture permeability,and none exceeds 3000mg per day per L.
Torque Applicable to Screw-Type Container
| Closure Diameter1(mm) | Suggested Tightness Range with Manually Applied Torque;2(inch-pounds) |
| 8 | 5 |
| 10 | 6 |
| 13 | 8 |
| 15 | 5–9 |
| 18 | 7–10 |
| 20 | 8–12 |
| 22 | 9–14 |
| 24 | 10–18 |
| 28 | 12–21 |
| 30 | 13–23 |
| 33 | 15–25 |
| 38 | 17–26 |
| 43 | 17–27 |
| 48 | 19–30 |
| 53 | 21–36 |
| 58 | 23–40 |
| 63 | 25–43 |
| 66 | 26–45 |
| 70 | 28–50 |
| 83 | 32–65 |
| 86 | 40–65 |
| 89 | 40–70 |
| 100 | 45–70 |
| 110 | 45–70 |
| 120 | 55–95 |
| 132 | 60–95 |
|
1
The torque designated for the next larger closure diameter is to be applied in testing containers having a closure diameter intermediate to the diameters listed.
2
Asuitable apparatus is available from Owens-Illinois,Toledo,OH43666.(Model 25torque tester is used for testing between 0and 25;Model 50for testing between 0and 50;and Model 100for testing between 0and 100inch-pounds of torque.)The torque values refer to application,not removal,of the closure.For further detail regarding instructions,reference may be made to “Standard Test Method for Application and Removal Torque of Threaded or Lug-Style Closures”ASTM Method D3198-97,published by the American Society for Testing and Materials,1916Race St.,Philadelphia,PA19103.
|
|
SINGLE-UNIT CONTAINERS AND UNIT-DOSE CONTAINERS FOR CAPSULES AND TABLETS
To permit an informed judgment regarding the suitability of the packaging for a particular type of product,the following procedure and classification scheme are provided for evaluating the moisture-permeation characteristics of single-unit and unit-dose containers.Inasmuch as equipment and operator performance may affect the moisture permeation of a container formed or closed,the moisture-permeation characteristics of the packaging system being utilized shall be determined.
Desiccant—
Dry suitable desiccant pellets2at 110for 1hour prior to use.Use pellets weighing approximately 400mg each and having a diameter of approximately 8mm.[NOTE—If necessary due to limited unit-dose container size,pellets weighing less than 400mg each and having a diameter of less than 8mm may be used.]
for 1hour prior to use.Use pellets weighing approximately 400mg each and having a diameter of approximately 8mm.[NOTE—If necessary due to limited unit-dose container size,pellets weighing less than 400mg each and having a diameter of less than 8mm may be used.]
Procedure—
Method I—
Seal not fewer than 10unit-dose containers with 1pellet in each,and seal 10additional,empty unit-dose containers to provide the controls,using finger cots or padded forceps to handle the sealed containers.Number the containers,and record the individual weights3to the nearest mg.Weigh the controls as a unit,and divide the total weight by the number of controls to obtain the average.Store all of the containers at 75±3%relative humidity and at a temperature of 23±2.[NOTE—Asaturated system of 35g of sodium chloride with each 100mLof water placed in the bottom of a desiccator maintains the specified humidity.Other methods may be employed to maintain these conditions.]After a 24-hour interval,and at each multiple thereof (see Results),remove the containers from the chamber,and allow them to equilibrate for 15to 60minutes in the weighing area.Again record the weight of the individual containers and the combined controls in the same manner.[NOTE—If any indicating pellets turn pink during this procedure,or if the pellet weight increase exceeds 10%,terminate the test,and regard only earlier determinations as valid.]Return the containers to the humidity chamber.Calculate the rate of moisture permeation,in mg per day,of each container taken by the formula:
.[NOTE—Asaturated system of 35g of sodium chloride with each 100mLof water placed in the bottom of a desiccator maintains the specified humidity.Other methods may be employed to maintain these conditions.]After a 24-hour interval,and at each multiple thereof (see Results),remove the containers from the chamber,and allow them to equilibrate for 15to 60minutes in the weighing area.Again record the weight of the individual containers and the combined controls in the same manner.[NOTE—If any indicating pellets turn pink during this procedure,or if the pellet weight increase exceeds 10%,terminate the test,and regard only earlier determinations as valid.]Return the containers to the humidity chamber.Calculate the rate of moisture permeation,in mg per day,of each container taken by the formula:
(1/N)[(WF–WI)–(CF–CI)],
in which Nis the number of days expired in the test period (beginning after the initial 24-hour equilibration period);(WF-WI)is the difference,in mg,between the final and initial weights of each test container;and (CF-CI)is the difference,in mg,between the average final and average initial weights of the controls,the data being calculated to two significant figures.[NOTE—Where the permeations measured are less than 5mg per day,and where the controls are observed to reach equilibrium within 7days,the individual permeations may be determined more accurately by using the 7-day test container and control container weights as WIand CI,respectively,in the calculation.In this case,a suitable test interval for Class A(seeResults)would be not less than 28days following the initial 7-day equilibration period (a total of 35days).]
Method II—
Use this procedure for packs (e.g.,punch-out cards)that incorporate a number of separately sealed unit-dose containers or blisters.Seal a sufficient number of packs,such that not fewer than 4packs and a total of not fewer than 10unit-dose containers or blisters filled with 1pellet in each unit are tested.Seal a corresponding number of empty packs,each pack containing the same number of unit-dose containers or blisters as used in the test packs,to provide the controls.Store all of the containers at 75±3%relative humidity and at a temperature of 23±2.[NOTE—Asaturated system of 35g of sodium chloride with each 100mLof water placed in the bottom of a desiccator maintains the specified humidity.Other methods may be employed to maintain these conditions.]After 24hours,and at each multiple thereof (see Results),remove the packs from the chamber,and allow them to equilibrate for about 45minutes.Record the weights of the individual packs,and return them to the chamber.Weigh the control packs as a unit,and divide the total weight by the number of control packs to obtain the average empty pack weight.[NOTE—If any indicating pellets turn pink during the procedure,or if the average pellet weight increase in any pack exceeds 10%,terminate the test,and regard only earlier determinations as valid.]Calculate the average rate of moisture permeation,in mg per day,for each unit-dose container or blister in each pack taken by the formula:
.[NOTE—Asaturated system of 35g of sodium chloride with each 100mLof water placed in the bottom of a desiccator maintains the specified humidity.Other methods may be employed to maintain these conditions.]After 24hours,and at each multiple thereof (see Results),remove the packs from the chamber,and allow them to equilibrate for about 45minutes.Record the weights of the individual packs,and return them to the chamber.Weigh the control packs as a unit,and divide the total weight by the number of control packs to obtain the average empty pack weight.[NOTE—If any indicating pellets turn pink during the procedure,or if the average pellet weight increase in any pack exceeds 10%,terminate the test,and regard only earlier determinations as valid.]Calculate the average rate of moisture permeation,in mg per day,for each unit-dose container or blister in each pack taken by the formula:
(1/NX)[(WF–WI)–(CF–CI)],
in which Nis the number of days expired in the test period (beginning after the initial 24-hour equilibration period);Xis the number of separately sealed units per pack;(WF-WI)is the difference,in mg,between the final and initial weights of each test pack;and (CF-CI)is the difference,in mg,between the average final and average initial weights of the control packs,the rates being calculated to two significant figures.
Results—
The individual unit-dose containers as tested in Method Iare designated Class Aif not more than 1of 10containers tested exceeds 0.5mg per day in moisture permeation rate and none exceeds 1mg per day;they are designated Class Bif not more than 1of 10containers tested exceeds 5mg per day and none exceeds 10mg per day;they are designated Class Cif not more than 1of 10containers tested exceeds 20mg per day and none exceeds 40mg per day;and they are designated Class Dif the containers tested meet none of the moisture permeation rate requirements.
The packs as tested in Method IIare designated Class Aif no pack tested exceeds 0.5mg per day in average blister moisture permeation rate;they are designated Class Bif no pack tested exceeds 5mg per day in average blister moisture permeation rate;they are designated Class Cif no pack tested exceeds 20mg per day in average blister moisture permeation rate;and they are designated Class Dif the packs tested meet none of the above average blister moisture permeation rate requirements.
With the use of the Desiccantdescribed herein,as stated for Method Iand Method II,after every 24hours,the test and control containers or packs are weighed;and suitable test intervals for the final weighings,WFand CF,are as follows:24hours for Class D;48hours for Class C;7days for Class B;and not less than 28days for Class A.
1
Suitable 4-to 8-mesh,anhydrous calcium chloride is available commercially as Item JT1313-1from VWR Scientific.Consult the VWR Scientific catalog for ordering information or call 1-800-234-9300.
2
Suitable moisture-indicating desiccant pellets are available commercially from sources such as Medical Packaging,Inc.,470Route 31,Ringoes,NJ08551-1409[Telephone 800-257-5282;in NJ,609-466-8991;FAX609-466-3775],as Indicating Desiccant Pellets,Item No.TK-1002.
3
Accurate comparisons of Class Acontainers may require test periods in excess of 28days if weighings are performed on a Class Aprescription balance (seePrescription Balances and Volumetric Apparatus á1176ñ).The use of an analytical balance on which weights can be recorded to 4or 5decimal places may permit more precise characterization between containers and/or shorter test periods.