Quality Control of Packaging Material for Parenteral Products PDF

1 Quality control test for packaging material of Parenteral products 2       Content Definition Types of packaging material Quality control test for Glass container Quality control test for Plastic container Quality control test for closures References Definition  Packaging is the sci...

1 Quality control test for packaging material of Parenteral products 2       Content Definition Types of packaging material Quality control test for Glass container Quality control test for Plastic container Quality control test for closures References Definition  Packaging is the science, art and technology of enclosing or protecting products for distribution, storage , sale and use. Packaging types Primary packaging Secondary packaging Tertiary packaging 5 6 TEST on containers QUALITY CONTROL TESTS FOR GLASS CONTAINERS A. Powdered glass test B. Water attack test C. Hydrolytic resistance test D. Arsenic test E. Thermal shock test F. Internal bursting pressure test G. Leakage test QUALITY CONTROL TEST FOR PLASTIC CONTAINERS A. Water vapour permeability B. Clarity or aqueous extract TYPES OF GLASS: TYPE I Neutral or borosilicate glass TYPE II Treated soda lime glass TYPE III Soda lime glass TYPE IV General purpose soda lime glass QUALITY CONTROL TESTS FOR GLASS CONTAINERS Powder glass test Done to estimate the amount of alkali leached from the powdered glass, which usually happens at elevated temperatures. Sample containers are rinsed with purified water and dried. 50 ml of purified water is added to the dried sample and autoclaved at 121°C for 30 mins and cooled and decanted. The containers are grinded in a mortar to a fine powder and passed through sieve no. 20 and 50. The decanted liquid is titrated with 0.02 N H2SO4 using methyl red as indicator. 10gm of the sample is washed with acetone and dried. (B) WATERATTCAK TEST (USP):  This test is performed on intact containers.  This is only for treated soda lime glass Principle: To determine whether the alkali leached from the surface of a container is within the specified limits or not. Since the inner surface is under test entire container (ampoule) has to be used. The amount of acid that is necessary to neutralize the released alkali from the surface is estimated. The leaching of alkali is accelerated using elevated temperature for a specified time. Methyl red indicator is used to determine the endpoint PROCEDURE TABLE : Types of glass and their test 13 of glass limits Types General Type of test description of glass I Highly resistant, Powdered glass Borosilicate glass II Treated lime glass soda- Water attack III Soda-lime glass Powdered glass IV General -purpose Powdered glass soda-lime glass Limits size , ml All Limits (ml of 0.02N) 1.0 100 or less 0.7 Over 100 All 0.2 8.5 All 15.0 HYDROLYTIC RESISTANCE OF GLASS CONTAINER Rinse each container at least 3 times with CO2 free water and fill with the same to their filling volume. fill & cover the vials and bottles and keep in autoclave. Heat to 100°C for 10min. & allow the steam to issue from the vent cork. Remove the container from autoclave, cool & combine the liquids being examined. Measure the volume of test solution into a conical flask and titrate with 0.01N HCL using methyl red as an indicator Perform blank with water and the difference between the titration represents the volume of HCl consumed by test solution Rise the temp. from 100°C to 121°C over 20min. Maintain the temp at 121°C to 122°C for 60min. Lower the temp from 121°C to 100°C over 40min. (D) ARSENIC TEST:  This test is for glass container intended for aqueous parenteral.Wash the inner and outer surface of container with fresh distilled water for 5min. pipette out 10ml solution from combined contents of all ampoules to the flask. Do the blank with 10 ml hydrogen molybdate. Determine the absorbance Add 10ml of HNO3 to dryness on the water bath, dry the residue in an oven at 130⁰C for 30min cool and add 10ml hydrogen molybdate reagent The absorbance of test should not exceed the absorbance of standard arsenic solution (10 ppm) Swirl to dissolve and heat under water bath and reflux for 25min. Cool to room temp and determine the absorbance at 840 nm. THERMAL SHOCK TEST Place the samples in upright position in a tray. Immense the tray into a hot water for a few time & transfers to cold water bath. Examine cracks or breaks before and after the test. A typical test uses 45°C temp. difference between hot and cold water. Small bottles withstand a temp. differential of 60 to 80°C . INTERNAL BURSTING PRESSURE TEST The test bottle is filled with water and placed inside the test chamber of “American glass research increment pressure tester” A scaling head is applied and internal pressure automatically raised by a series of increment each of which is held for a set of time. The bottle can be checked to a preselected pressure level and the test continues until the container finally bursts. 18 https://www.youtube.com/watch?v=3eKvRTPpDsw LEAKAGE TEST : Drug fill container is placed in a container filled with coloured solution Which is at high pressure compared to the pressure inside the glass container so that the coloured solution enters the container if any cracks or any breakage is present. So leakage is there. QUALITY CONTROL TESTS FOR CLOSURES 20 Preparation of sample: • The closures are washed in 0.2% w/v of anionic surface active agents for 5 mins. • Rinsed five times with distilled water and 200ml water is added. • Subjected to autoclave at 119°C to 123°C for 20-30 mins covering with aluminum foil. • Cooled and solution is separated from closures (Solution A). 1. Residue on evaporation: • 50ml of Solution A is evaporated to dryness on a water bath and driedat 105°C. • The residue weighs not more than 4 mg. 2. Sterilisation test: 21 The closures used for the preparation of the sample solution shall not soften or become tacky and there shall be no visual change in the closure. 3. pH of aqueous extract: To 20ml of solution A, 0.1ml of bromothymol blue solution is added. ↓ NMT 0.3ml of 0.01M NaOH or 0.8ml of 0.01M HCl is rqd. to change the color of the solution to blue or yellow respt. 4. Self stability test: Pierced ten times with hypodermic needle ↓ Immersed in 0.1% methylene blue solution and subjected to a pressure of about 27 KPa ↓ Restored to ATM pressure and made to stand for 30mins ↓ Traces of colored solution should not be found. QUALITY CONTROL TEST FOR PLASTIC CONTAINERS 24 Plastic containers are light in weight and non-breakable, but they have high permeability for water vapour. pharmacopoeia prescribes Leakage test for plastic containers., These test are applicable for both injectable and non-injectable. Water vapour permeability test is applicable for injectable preparation. (A)WATER VAPOUR PERMEABILITY (Applicable for injectable 25 preparation): Fill 5 containers with normal volume of water and seal the bottle with aluminium foil Weigh each container Allow to stand for 14days at RH of 60 ±5% at 20ׄ° to 25°C Reweigh the container and check loss of weight in each container should not be more than 0.2% (C)CLARITY OF AQUEOUS EXTRACT: 26  Select unlabelled portion from a suitable containers Cut these portions into strips and Wash it with extraneous matter by shaking with two separate portions of distilled water for about 20sec.  after Transfer to flask – previously washed with chromic acid mixture and rinsed with distilled water add 250ml distilled water and Cover the flask and autoclave at 121°C, 30min.  carry out the blank determination using 250ml dist. Water.  Cool and examine the extract, it should be Colourless & free from turbidity. Sterile product validation:Product and pack compatibility The components must be washed and sterilized through a validated procedure.  The vials must be filled with the sterile product under sterile conditions and terminally sterilized if this is a part of the intended product operation. Component performance should be monitored during the compatibility trials to ensure that deterioration has not occurred. Seal integrity  The seals of each vial should be examined before the experiment to ensure that there are no defectives.  each vial should be inserted into a tray containing the challenge bacteria. The samples should be cycled through temperature and pressure changes expected on the market for several weeks.  Careful cleaning of the vials and examination of contents for sterility will determine the seal quality Light transmissionThis test is to determine the effect of light passing through the bottle wall on the product stability and appearance. The bottle wall thickness can have a significant effect on the results obtained. 30 THE END