3.2.9. RUBBER CLOSURES FOR CONTAINERS FOR …

1 RUBBER CLOSURES for containersEUROPEAN PHARMACOPOEIA oil. Calculate the internal surface area of a syringe insquare centimetres using the following expression:V=nominal volume of the syringe, in cubic centimetres;h=height of the graduation, in a sufficient number of syringes to give an internal surfacearea of 100 cm2to 200 cm2. Aspirate into each syringe avolume ofmethylenechlorideRequal to half the nominalvolume and make up to the nominal volume with air. Rinse theinternal surface corresponding to the nominal volume with thesolvent by inverting the syringe ten times in succession withthe needle fitting closed by a finger covered by a plastic filminert to methylene chloride. Expel the extracts into a tared dishand repeat the operation.

2 Evaporate the combined extracts not more than mg per square centimetre of internalsurface the residue by infrared absorption spectrophotometry( ). It shows absorption bands typical of silicone oil at805 cm 1,1020cm 1,1095cm 1, 1260 cm 1and 2960 cm acid Rand mL M iodide Rand titrate immediately Msodium thiosulfateusing mL ofstarch solution Rasindicator. Carry out a blank titration using mL ofwater forinjections R. The difference between the titration volumes isnot greater than Fill a syringe withwater R(blank) and fillanother with a 1 in 10 dilution of primary opalescent suspension( ). Use primary opalescent suspension that has beenallowed to stand at 20 2 C for 24 h before use.

3 Compare withthe naked eye in diffused light against a dark background. Theopalescence of the suspension is detectable when comparedwith the ( ).Syringes stated to be sterile comply withthe test for sterility carried out as , open the package, withdraw the syringe, separate thecomponents and place each in a suitable container containingsufficient culture media to cover the part completely. Use boththe recommended media ( ).Syringes stated to be sterile only internally comply with thetest for sterility carried out as follows. Use 50 mL of inoculationmedium for each test syringe. Using aseptic technique, removethe needle protector and submerge the needle in the culturemedium. Flush the syringe five times by withdrawing theplunger to its fullest ( ).

4 Syringes with a nominal volume equal toor greater than 15 mL comply with the test for pyrogens. Filla minimum of three syringes to their nominal volume with apyrogen-free 9 g/L solution ofsodium chloride Rand maintainat a temperature of 37 C for 2 h. Combine the solutionsaseptically in a pyrogen-free container and carry out the testimmediately. Inject per kilogram of the rabbit s mass 10 mL ofthe label on thepackagestates: the batch number; adescriptionofthesyringe; that the syringe is for single-use label on theouter packagestates: the method of sterilisation; that the syringe is sterile or that it is sterile only internally; the identity of the manufacturer; that the syringe is not to be used if the packaging is damagedor the sterility protector is :30209corrected RUBBER CLOSURES FORCONTAINERS FOR AQUEOUSPARENTERAL PREPARATIONS,FOR POWDERS AND FORFREEZE-DRIED POWDERSR ubber CLOSURES for CONTAINERS for aqueous parenteralpreparations for powders and for freeze-dried powders aremade of materials obtained by vulcanisation (cross-linking)of macromolecular organic substances (elastomers), withappropriate additives.

5 The specification also applies to closuresfor CONTAINERS for powders and freeze-dried products to bedissolved in water immediately before use. The specificationdoes not apply to CLOSURES made from silicone elastomer (whichare dealt with elastomer for CLOSURES andtubing), to laminated CLOSURES or to lacquered CLOSURES . Theelastomers are produced from natural or synthetic substancesby polymerisation, polyaddition or polycondensation. Thenature of the principal components and of the various additives(for example vulcanisers, accelerators, stabilisers, pigments)depends on the properties required for the finished CLOSURES may be classified in 2 types: type I closuresare those which meet the strictest requirements and whicharetobepreferred.

6 TypeIIclosuresarethosewhich,havingmechan ical properties suitable for special uses (for example,multiple piercing), cannot meet requirements as severe as thosefor the first category because of their chemical CLOSURES chosen for use with a particular preparation aresuch that: the components of the preparation in contact with theclosure are not adsorbed onto the surface of the closureanddonotmigrateintoorthroughthecl osuretoanextentsufficient to affect the preparation adversely, the closure does not yield to the preparation substances inquantities sufficient to affect its stability or to present a riskof CLOSURES are compatible with the preparation for which theyare used throughout its period of manufacturer of the preparation must obtain from thesupplier an assurance that the composition of the closure doesnot vary and that it is identical to that of the closure usedduring compatibility testing.

7 When the supplier informs themanufacturer of the preparation of changes in the composition,compatibility testing must be repeated, totally or partly,depending on the nature of the CLOSURES are washed and may be sterilised before CLOSURES are elastic; they are translucent or opaqueand have no characteristic colour, the latter depending on theadditives used. They are practically insoluble in tetrahydrofuran,in which, however, a considerable reversible swelling may are homogeneous and practically free from flash andadventitious materials (for example fibres, foreign particles,waste RUBBER ).Identification of the type of RUBBER used for the CLOSURES isnot within the scope of this specification. The identificationtest given below distinguishes elastomer and non-elastomerclosures but does not differentiate the various types ofrubber.

8 Other identity tests may be carried out with the aimof detecting differences in a batch compared to the closuresused for compatibility testing. One or more of the followinganalytical methods may be applied for this purpose:374 See the information section on general monographs (cover pages)EUROPEAN PHARMACOPOEIA RUBBER CLOSURES for containersdetermination of relative density, determination ofsulfated ash, determination ofsulfurcontent,thin-layerchromatography carried out on an extract, ultravioletabsorption spectrophotometry of an extract, infraredabsorption spectrophotometry of a The elasticity is such that a strip of material with across-section of 1 mm2to 5 mm2can be stretched by hand toat least twice its original length.

9 Having been stretched totwice its length for 1 min, it contracts to less than timesits original length within 30 Heat 1 g to 2 g in a heat-resistant test-tube over an openflametodrythesampleandcontinueheatin guntilpyrolysatevapours are condensed near the top edge of the a few drops of the pyrolysate on a potassium bromidedisc and examine by infrared absorption spectrophotometry( ), comparing with the spectrum obtained with thetype The total ash ( )iswithin 10percentoftheresultobtained with the type samples to be analysed may be washed and sterilisedbefore S. Introduce a number of uncut CLOSURES correspondingto a surface area of about 100 cm2in a suitable glass container,cover withwater for injections R, boil for 5 min and rinse5timeswithcoldwater for injections in a wide-necked flask (glass type I, ), add 200 mLofwater for injections Rand weigh.

10 Cover the mouth of theflask with a borosilicate-glass beaker. Heat in an autoclave sothatatemperatureof121 2 Cisreachedwithin20minto30 min and maintain at this temperature for 30 min. Cool toroom temperature over about 30 min. Make up to the originalmass withwater for injections R. Shake and immediatelyseparate the solution from the RUBBER by decantation. Shakesolution S before each testBlank. Prepare a blank in the same manner using 200 mL ofwater for injections of solution. Solution S is not more opalescentthan reference suspension II for type I CLOSURES and is not moreopalescent than reference suspension III for type II CLOSURES ( ). Solution S is not more intensely coloured than referencesolution GY5( , Method II).