Volume-5, Issue-4, Oct-2014 Available Online at International Journal Of Pharma Professional s Research Review Article

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1 Available Online at International Journal Of Pharma Professional s Research Review Article A REVIEW ON GLASS CONTAINERS USED AS PHARMACEUTICAL PACKAGING MATERIALS Pawan Jalwal* 1, Sandeep Kumar 2, Ramchander Khatri 3, ISSN NO: Tanuj Hooda 3 1.Shri Baba Mast Nath Institute of Pharmaceutical Science and Research, Asthal Bohar, Rohtak 2.Indswift, Mankumajra, Solen, Himachal Pradesh 3.Faculty of Pharmacy, Vaish Institute of Pharmaceutical Education and Research, Rohtak, Haryana Abstract Since time immemorial, glass has been the preferred container material for pharmaceutics. Its current market share for primary packaging of injectables ranges at 98 %; every year more than 23 billion primary containers made from glass for parenterals like ampoules, vials or prefillable syringes are produced and used worldwide. Glass is one of the oldest materials known to man. Stone-age civilizations already used shards of natural glass as cutting tools. Around 3500 BC, man began to produce glass himself by melting a mixture of sand, soda and lime. Later the blowing of glass was discovered and made glass vessels widely available. Glass owes its popularity as a material for pharmaceutical containers to a product of desirable characteristics. It is durable, inert, clean and transparent. Anyhow, even the best material is challenged from time to time often just to prove that there is no superior alternative. At the moment, delamination is a much-discussed issue, as new, highly efficient but aggressive drug products set increased demands for their primary containers. Keywords: - : Glass, container, Pharmaceutical Packaging etc. Introduction Packaging may be defined as the process by which the pharmaceutical dosage forms are suitably placed so that they should retain their therapeutic effectiveness approved. They must not be reactive with the product and shows compatibility. They must not impart tastes or odors to the products. They must meet applicable tamper-resistance requirements and adaptable to from the time of their packaging till they are commonly employed high-speed packaging consumed. Packing consists of enclosing an equipment. They must have reasonable cost in individual item or several items in a container usually for shipment or delivery. This operation is mostly relation to the cost of the product. They must show resistance to moisture, corrosion by acid and alkali, done by hand and machine. Packaging system divided grease, microorganism, insects and rodents, into three parts; one is primary system, second is secondary system and third is tertiary system. Primary package system is made up of those package components & subcomponents that come into direct contact with the product or those that may have a temperature etc. there are number of packaging materials used for the construction of containers and closures for the pharmaceutical purposes like glass, metals, rubber and plastic etc. Glass direct effect on the product shelf life. Secondary or Glass is commonly used in pharmaceutical tertiary package system includes cartons, corrugated shippers & pallets. packaging because it possesses superior protective qualities. Glass containers for pharmaceutical use are Criteria for the selection of Packaging Material intended to come into direct contact with The materials selected for packaging must protect the pharmaceutical preparations. Glass used for preparation from environmental conditions and maintain its stability. The material should be FDA pharmaceutical containers is either a borosilicate glass or a soda lime glass. It is made up of silica with 1150

2 varying amount of metal oxides, soda-ash, limestone, and cullet. The sand is almost pure silica (SiO2); the soda-ash is sodium carbonate (Na2CO3), and the limestone calcium carbonate (CaCO3). Cullet is broken glass that is mixed with the batch and acts as a fusion agent for the entire mixture. The composition of glass varies and is usually adjusted for specific purposes. The most common cations found in pharmaceutical glassware are silicon, aluminum, boron, sodium, potassium, calcium, magnesium, zinc, and barium. The only anion of consequence is oxygen. The properties of the glass depend on the elements presents in its compositions. Reduction in the proportion of sodium ions makes glass chemically resistant; however, without sodium or other alkalies, glass is difficult to melt and is expensive. Boron oxide is incorporated mainly to aid in the melting process through reduction of the temperature required. Lead in small traces gives clarity and brilliance, but produces a relatively soft grade of glass. Alumina (aluminum oxide) is often used to increase the hardness and durability and to increase resistance to chemical action. Preparation of glass Glass is composed principally of sand (silica - SiO2), soda-ash (Na2CO3 - sodium carbonate) and lime-stone (CaCO3-calcium carbonate).glass made from pure silica consists of a three-dimensional network of silicon atoms each of which is surrounded by four oxygen atoms and in this way the tetrahedral are linked together to produce the network. Glass prepared from pure silica require very high temperature to fuse, hence soda-ash and lime is used to reduce the melting point. Glass made of pure silica has network very hard and chemically resistant but melting point is very high so it is very difficult to mould. When the addition of Na2O in pure silica; the structure is less rigid and melting point is low and easier to mould. This type of glass is rapidly attacked by water and NaOH is leached out of the glass. When the addition of any oxide with pure silica like CaO, BaO, MgO, PbO and ZnO then divalent oxides do not break the network of pure silica, but only push the tetrahedron apart. It is more rigid than soda-silica network. Since the bond is stronger, hence chemical reactivity is lowered. When boric oxide (B2O3) or aluminium oxide (Al2O3) having trivalent valency combined with the pure silica; since boric oxide, like silica, is acidic, it does not disrupt the network of silica but forms tetrahedron itself; however, these are not the same size as the silicon tetrehedra; as a result the lattice becomes distorted, and this produces flexibility. It is highly chemically resistant. 1151

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4 Type I Borosilicate Glass Borosilicate glass contains a significant amount of boric oxide, aluminum oxide, and alkali and /or alkaline earth oxides. Borosilicate glass has a high hydrolytic resistance due to the chemical composition of the glass itself. In this type of glass boron, aluminium and zinc replace the substantial part of the alkali and earth cations. It is more chemically inert than the soda-lime glass which contains either none or an insignificant amount of these cations. This glass is used to contain strong acids and alkalies as well as all types of solvents. It has a definite and measurable chemical reaction with some substances notably water. The water shows leaching properties by the leaching of loosely bound sodium with silicon from the surface of glass. When the distilled water stored for one year in flint type III glass picks up 10 to 15 parts per million (ppm) of sodium hydroxide along with traces of other ingredients of the glass. The addition of approximately 6% boron to form type I glass reduces the leaching action, so that only 0.5 ppm is dissolved in a year. Type II Treated Soda-Lime Glass Type II containers are made of commercial soda-lime glass that has been de-alkalized or treated to remove surface alkali. This process is known as "sulfur treatment" and virtually prevents "weathering" of empty bottles. The treatment offered by several glass manufacturers exposes the glass to an atmosphere containing water vapor and acidic gases, particularly sulfur dioxide at an elevated temperature. Sulfur treatment neutralizes the alkaline oxides on the surface thereby rendering the glass more chemically resistant. Type III Regular Soda-Lime Glass Containers are untreated and made of commercial soda-lime glass of average or better-than average chemical resistance. Type NP General-Purpose Soda-Lime Glass Containers made of soda-lime glass are supplied for non-parenteral products, those intended for oral or topical use 1153

5 Process involved in Manufacturing of Glass Four basic processes are used in the production of glass: blowing, drawing, pressing, and casting. Blowing uses compressed air to form the molten glass in the cavity of a metal mold. Most commercial bottles and jars are produced on automatic equipment by this method. In drawing, molten glass is pulled through dies or rollers that shape the soft glass. Rods, tubes, sheet glass, and other items of uniform diameter are usually produced commercially by drawing. Ampoules, cartridges and vials drawn from tubing have a thinner more uniform wall thickness with less distortion than blow-molded containers. In pressing mechanical force is used to press the molten glass against the side of a mold. Casting uses gravity or centrifugal force to initiate the formation of molten glass in the cavity. Colored Glass - Light Protection Glass containers for drugs are generally available in clear flint or amber color. For decorative purposes, special colors such as blue, emerald green and opal may be obtained from the glass manufacturer. Only amber glass and red glass are effective in protecting the contents of a bottle from the effects of sunlight by screening out harmful ultraviolet rays. The USP specifications for light-resistant containers require the glass to provide protection against 2900 to 4500 Angstroms of light. Amber glass meets these specifications, but the iron oxide added to produce this color could leach into the product. Therefore, if the product contains ingredients subject to ironcatalyzed chemical reactions, amber glass should not be used. Manganese oxide can also be used for amber glasses. Evaluation of glass containers Instrument and reagents used for test For these tests there are various instruments are used 1154

6 for their conduction. Autoclave, Mortar and pestle, sieves having 20, 40 and 50 sieves number made up of stainless steel, Conical flask having 250 ml made of resistant glass aged as specified, A 900 g hammer, a permanent magnet, a desiccator and an adequate volumetric apparatus are used. There are various reagents used for the conduction of these test. High purity water having conductivity 25 is used. There must also be an assurance that this water is not contaminated by copper or its products (e.g., copper pipes, stills, or receivers). This water may be prepared by passing distilled water through a deionizer cartridge packed with a mixed bed of nuclear grade resin, then through a cellulose ester membrane having opening not exceeding 0.45 µm. Methyl Red solution (powdered glass test and water attack at 121 ) dissolve 24 mg of methyl red sodium in purified water to make 100 ml. if necessary, neutralize the solution with 0.02 N sodium hydroxide, or acidify it with 0.02 N sulfuric acid so that the titration of 100 ml of high purity water, containing 5 drops of indicator, does not require more than ml. of N sodium hydroxide to effect the color change of the indicator, which should occur at the ph of 5.6. Methyl Red solution (surface glass test) dissolve 50 mg of methyl red solution in 1.86 ml of 0.1 M sodium hydroxide and 50 ml of ethanol and dilute to 100 ml with purified water. To test for sensitivity, add 100 ml of carbon dioxide free water and 0.05 ml of 0.02 M hydrochloric acid to 0.1 ml of the methyl red solution (the solution should be red). Not more than 0.1 ml of 0.02 M sodium hydroxide is required to change the color to yellow. Color change: ph 4.4 (red) to ph 6.0 (yellow). Surface glass test Determination of the filling volume The filling volume is the volume to be filled with purified water in the container for the purpose of the test. For vials and bottles the filling volume is 90% of the brimful capacity. For ampoules it is the volume up to the height of the shoulder. In case of vials and bottle select randomly 6 containers from the sample lot or 3 if their capacity exceeds 100 ml and remove the dirt. Weigh the empty containers with an accuracy of 0.1 g. place the containers on a horizontal surface, and fill them with purified water to about the rim edge avoiding overflow and introduction of air bubbles. Adjust the liquid levels to the brimful line. Weigh the filled containers to obtain the mass of the water expressed to 2 decimal places for containers having a nominal volume less or equal to 30 ml and expressed to 1 decimal place for containers having a nominal volume greater than 30 ml. calculate the mean value of the brimful capacity in ml and multiply it by 0.9. This volume expressed to 1 decimal place is the filling volume for the particular containers lot. In case of ampoules place at least 6 dry ampoules on a flat horizontal surface and fill them with purified water from a burette until the water reaches at the shoulder level where the body of the ampoule decreases to the shoulder of the ampoule. Read the capacities expressed to 2 decimal places and calculate the mean value. This volume expressed to 1 decimal place is the filling volume for the particular ampoule lot. The filling volume may also be determined by weighing. The determination is carried out on unused containers. The volumes of the test liquid necessary for the final determination are indicated in the table. Cleaning Remove any debris or dust. Shortly before the test, rinse each container carefully at least twice with purified water, and allow standing. Immediately before testing, empty the containers rinse once with purified water, then with carbon dioxide free water and allow draining. Complete the cleaning procedure from the first rinsing in not less than 20 minutes and not more than 25 minutes. Heat closed ampoules in a 1155

7 water bath or in an air oven at about 50 for approximately 2 minutes before opening. Do not rinse before testing. Filling and heating The containers are filled with carbon dioxide free water up to the filling volume. Containers in the form of cartridges or prefilled syringes are closed in a suitable manner with material that does not interfere with the test. Each container, including ampoules, shall be loosely capped with an inert material such as a dish of neutral glass or aluminum foil previously rinsed with purified water. Place the containers on the tray of the autoclave. Place the tray in the autoclave containing a quantity of water such that the tray remains clear of the water. Close the autoclave, and carry out the following operations: 1. Heat the autoclave to 100 and allow the steam to issue from the vent cock for 10 minutes 2. Close the vent cock and raise the temperature from 100 to 121 at a rate of 1 per minutes 3. Maintain the temperature at 121 ±1 for 60±1 minutes 4. Lower the temperature from 121 to 100 at a rate of 0.5 per minute, venting to prevent a vacuum 5. Do not open the autoclave before it has cooled down to Remove the containers from the autoclave using normal precautions, place them in a water bath at 80, and run cold tap water, taking care that the water does not contact the loose foil caps to avoid contamination of the extraction solution 7. Cooling time does not exceed 30 minutes 8. The extraction solutions are analyzed by titration according to the method described below. Method Carry out the titration within 1 hour of removal of the containers from the autoclave. Combine the liquids obtained from the containers, and mix. Introduce the prescribed volume indicated in table below in to a conical flask. Place the same volume of carbon dioxide free water into a second similar flask as a blank. Add 0.05 ml of methyl red solution to each flask for each 25 ml of liquid. Titrate the blank with 0.01 M hydrochloric acid. Titrate the test liquid with the dame acid until the color of the resulting solution is the same as that obtained for the blank. Subtract the value found for the blank titration from that found for the test liquid, and express the results in ml of 0.01 M hydrochloric acid per 100 ml. express titration values of less than 1.0 ml to 2 decimal places and titration values of more than or equal to 1.0 ml to 1 decimal place. Limits: The results, or the average of the results if more than one titration is performed, are not greater than the values stated in table. Powdered Glass Test The containers to be tested are initially rinsed with water and dried in hot air oven. At least three containers are taken and broken with a hammer to get coarse fragments of about 100g size of the largest fragment should not be greater than 25mm and divide the coarsely crushed glass into three approximately equal portions and place one the portion to a mortar and insert the pestle and strike heavily once with the hammer. Transfer the contents of the mortar to the coarsest sieve. Repeat the operation sufficient number of times until the entire 1156

8 fragment has been transferred to the sieve. The glass is sifted and the portion retained by the No. 20 and No. 40 sieve is taken and are further fractured. Shake the nest of sieve manually or mechanically for 5 minutes. Transfer the portion retained on the No. 50 sieve, which should weigh in excess of 10 gm to a closed container and store in a desiccators until used for the test. Spread the specimen on a piece of glazed paper and pass a magnet through it to remove particles of iron that may be introduced during the crushing. Transfer the specimen to a 250 ml conical flask of resistant glass and wash it with six 30 ml portions of acetone swirling each time for about 30 seconds and carefully decanting the acetone. After washing the specimen should be free from agglomerations of glass powder and the surface of the grains should be practically free from adhering fine particles. Dry the flask and contents for 20 minutes at 140 transfer the grains to a weighing bottle and cool in desiccators. Use the test specimen within 48 hours after drying. Procedure Transfer gm of the prepared specimen accurately weighed to a 250 ml conical flask that has been digested (aged) previously with high purity water in a bath at 90 for at least 24 hours or at 121 for 1 hour. Add 50.0 ml of high purity water to this flask and to one similarly prepared to provide a blank. Cap all flasks with borosilicate glass beakers that previously have been treated as described for the flasks and that are of such size that the bottoms of the beakers fit snugly down on the top rims of the containers. Place the containers in the autoclave, and close it securely, leaving the vent cock open. Heat until steam issues vigorously from the vent cock, and continue heating for 10 minutes. Close the vent cock, and adjust the temperature to 121, taking 19 to 23 minutes to reach the desired temperature. Hold the temperature at 121± 2.0 for 30 minutes, counting from the time this temperature is reached. Reduce the heat so that the autoclave cools and comes to atmospheric pressure in 38 to 46 minutes, being vented as necessary to prevent the formation of a vacuum. Cool the flask at once in running water, decant the water from the flask into a suitably cleansed vessel,and wash the residual powdered glass with four 15 ml portions of high purity water, adding the decanted washings to the main portion. Add 5 drops of methyl red solution, and titrate immediately with N sulfuric acid. If the volume of titrating solution is expected to be less than 10 ml, use a micro burette. Record the volume of N sulfuric acid used to neutralize the extract from 10 gm of the prepared specimen of glass, corrected for a blank. The volume does not exceed that indicted in table for the type of glass concerned. Water attack at 121 The water attack at 121 test can be used to qualify type II glass. Rinse thoroughly 3 or more containers, selected at random, twice with high purity water. Procedure Fill each container to 90% of its overflow capacity with high purity water, and proceed as directed for procedure under powdered glass test, beginning with cap all flasks, except that the time of autoclaving shall be 60 minutes instead to 30 minutes, and ending with to prevent the formation of a vacuum. Empty the contents from 1 or more containers into a 100 ml graduated cylinder, combining, in the case of smaller containers, the contents of several containers to obtain a volume of 100 ml. place the pooled specimen in a 250 ml conical flask of resistant glass, add 5 drops of methyl red solution, and titrate, while warm, with N sulfuric acid. Complete the titration within 60 minutes after opening the autoclave. Record the volume of N sulfuric acid used, corrected for a blank obtained by titrating 100 ml of high purity water at the same temperature 1157

9 and with the same amount of indicator. The volume does not exceed that indicated in table. Reference 1.Garrett, E.R.: J. Pharm. Sci., 51:35, Levy, G.: J. Pharm, Sci., 50:429, Dimbley, V.: J. Pharm. And Pharmacol., 5.:969, Boddapati, S., and Butler, D. L., Im,S,and DeLuca, P.P.: J.Pharm. Sci., 69:608, Sarrut, S., and Nezelof, C.: Presse Med., 68:375, Vanga, S. V.: J. Parent. Drug. Assoc., 33:61, Moretti, C.: Boll Chem. Farm. 103:69, Correspondence Address: Pawan Jalwal Reader Faculty of Pharmaceutical Sciences, Baba Mastnath University, Asthal Bohar, Rohtak - Phone: Lipper, R.A., and Nevola, M.M..: Influence of Amber Glass on the Decomposition of Thiomerosol in Aqueous solution. In press. 9.Enever, R.P., and LiWanPo, A., and Schotton, E.: J.Pharm.Sci., 66:1087, Kassem, M.A.,Kassem, A.,A., and Ammar, H.O.: Pharm.Acta Helv., 44:611, European Pharmacopoeia 5.0, Glass containers for pharmaceutical use 01,6th edition 12.United State Pharmacopoeia XIX. Mack Publishing, Eastron, PA D. e. McDonald, Am. J. Hosp. Pharm. 29: (1972). 14.J. w. dietrich, Am. J. Hosp. Pharm. 30: (1973). 15.S. turco and R. E. king, Sterile Dosage Forms, Their Preparation and Clinical Application, Lea & Febiger, Philadelphia, P. moorhatch and W. L. chiou, Am. J. Hosp. Pharm. 31: (1974). 17.P. moorhatch and W. L. chiou, Am. J. Hosp. Pharm. 31: (1974). 1158