You are hereReview on: THE PHARMACEUTICAL PACKAGING

Review on: THE PHARMACEUTICAL PACKAGING


6)Containers:  
6.1-Glass containers
Glass is commonly used in pharmaceutical packaging because it possesses superior protective qualities.
Advantages:
•    Economical
•    Readily available container of variety of sizes and shapes
•    Impermeability
•    Strength and rigidity
•    Has FDA clearance
•    Does not deteriorate with age
•    Easy to clean
•    Effective closure and resolves are applicable.
•    Colored glass, especially amber, can give protection against light when it is required.
Disadvantages:
•    Fragility
•    Heavy weight

6.1.1-Composition of Glass:
Glass is composed principally of silica with varying amount of metal oxides, soda-ash, limestone, and cullet. The sand is almost pure silica, the soda-ash is sodium carbonate, and the limestone, calcium carbonate. 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. Many useful properties of glass are affected by the kind of elements it contains. 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), however, is often used to increase the hardness and durability and to increase resistance to chemical action.8

6.1.2-Manufacture 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 drawm 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.

6.1.3-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 iron-catalyzed chemical reactions, amber glass should not be used. Manganese oxide can also be used for amber glasses.

6.1.4-Glass for Drugs:
The USP and NF describe the various types of glass and provide the powdered glass and water attack tests for evaluating the chemical resistance of glass. The test results are measures of the amount of alkalinity leached from the glass by purified water under controlled elevated temperature conditions. The powdered glass test is performed on crushed glass of a specific size, and the water attack test is conducted on whole containers. The water attack test is used only with type II glass that has been exposed to sulfur dioxide fumes under controlled conditions.

6.1.4.1-Type I—Borosilicate Glass:
Borosilicate Glass is a highly resistant glass. In this type of glass a substantial part of the alkali and earth cations are replaced by boron and/or aluminum and zinc. It is more chemically inert than the soda-lime glass, which contains either none or an insignificant amount of these cations. Although glass is considered to be a virtually inert material and 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 sodium is loosely combined with the silicon and is leached from the surface of the glass by water. Distilled water stored for one year in flint type III glass (to be described) 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 borosilicate glass reduces the leaching action, so that only 0.5 ppm is dissolved in a year.

6.1.4.2-Type II—Treated Soda-Lime Glass:
When glassware is stored for several months, especially in a damp atmosphere or with extreme temperature variations, the wetting of the surface by condensed moisture (condensation) results in salts being dissolved out of the glass. This is called "blooming" or "weathering," and in its early stages, it gives the appearance of fine crystals on the glass. At this stage, these salts can be washed off with water or acid. Type II containers are made of commercial soda-lime glass that has been de-alkalized, or treated to remove surface alkali. The de-alkalizing 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. This results in a reaction between the gases and some of the surface alkali, rendering the surface fairly resistant, for a period of time, to attack by water. The alkali removed from the glass appears on the surface as a sulfate bloom, which is removed when the containers are washed before filling. Sulfur treatment neutralizes the alkaline oxides on the surface, thereby rendering the glass more chemically resistant.

6.1.4.3-Type III—Regular Soda-Lime Glass:
Containers are untreated and made of commercial soda-lime glass of average or better-than-aver-age chemical resistance.

6.1.4.4-Type NP—General-Purpose Soda-Lime Glass:
Containers made of soda-lime glass are supplied for nonparenteral products, those intended for oral or topical use.

6.1.5-Ampoules:
     Ampoules are thin-walled glass containers, which after filling, are sealed by either tip sealing or pull sealing. The contents are withdrawn after rupture of the glass, or a single occasion only. These are great packaging for a variety of drugs. The filed – in product is in contact with glass only and the packaging is 100% tamper proof. The break system OPC(one –point cut) or the color break ring offer consistent breaking force. There are wide variety of ampoule types from 0.5 to 50ml. Up to 3 color rings can be placed the stem or body for identification purpose. Printed ampoules with heavy metal free colors are available. Some of them are:
•    Type B straight –stem
•    Type C funnel –tip
•    Type D closed
   PHOTO 6.1:-DIFFERENT TYPES OF AMPOULES
6.1.6.Bottles, vials and syringes:
These are more or less thick walled containers with closures of glass or of material other than glass such as plastic materials or elastomers. The contents may be removed in several proportions on one of or more occasions.9

6.1.7-Test for glass containers:
 Test for surface hydrolytic resistance:
     Surface hydrolytic resistance test is conducted on unused glass containers. The number of containers to be examined and the volume of the test humid necessary for final determination are indicated in the following table(2) .
Table 6.1:

Nominal capacity of container  

Number of containers to b e used  

Volume of test solution to be used for titration ml 

3 or less  

At least 10 

25.0 

3 to 30 

At least 5 

50.0 

More than 30 

At least3 

100.0 

Initially each container is rinsed three times carefully with carbon dioxide free water. Then the container is allowed to drain and it is filled with the carbon dioxide free water to the required volume. If vials and bottle are used they are covered with neutral glass dishes or aluminum foil which is previously rinsed with carbon dioxide free water. If ampoules are used, they are sealed by heat fusion. The containers are then placed on the tray of the autoclave a containing a quantity of water in such a way that the tray remains clear and temperature is maintained between 100oC to 120o C over 20minutes. Then the temperature is adjusted between 120o-1220C for 60 minutes and finally the temperature is lowered from 120oC for 40 minutes. Remove the containers from the autoclave once the pressure reaches the atmospheric pressure and cool under running tap water Combine the liquids obtained from the containers being examined. The following titration should be carried out within 1 hour after removing the container from the autoclave. Introduce the prescribed volume of liquid in to a conical flask. Add 0.05ml of methyl red solution for each 20ml liquid. Titrate with 0.01M hydrochloric acid taking as the end point the color obtained by repeating the operation using the same volumes of carbon dioxide free water. The result is not greater than the volume state in table (3).


Table 6.2:

Capacity of container  

Volume of 0.01M hydrochloric acid VS per 100 ml of test solution


Type 1 or II glass ml 

Type III glass ml

Not more than 1 

3.0 

20.0 

More than 1 but not more than 2 

1.8 

17.6 

More than 2 but not more than 5 

1.3 

13.2 

More than 5 but not more than 10 

1.0 

10.2 

More than 10 but not more than 20 

0.80 

8.1 

More than 20 but not more than 50 

0.60 

6.1 

More than 50 but not more than 100

0.50 

4.8 

More than 100 but not more than 200 

0.40 

3.8 

More than 200 but not more than 500 

0.30 

2.9 

More than 500  

0.20 

2.2 

6.1.8-Test for hydrolytic resistance of powdered glass :
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. Transfer a part of the sample 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 all the fragment have been transferred to the sieve. The glass is sifted and the portion retained by the 710{mu)m and 423 {mu)m sieve are taken and are further fractured. The operation is respected until 20g of glass is retained by the 710{mu)m sieve. Rejected this portion and the portion that passes through 250{mu)m sieve. Shake the nest of sieve manually or mechanically for 5 minutes. Glass grains that passes through 425{mu)m sieve is taken metal particles are removed by suspending the glass grains in acetone the supernatant liquid is decanted the operation is repeated five times glass grains are speeded on an evaporating dish and allow the acetone to evaporating by drying in an oven at 110oC for 20minutes and allow to cool.
     20g of the glass grains to treated is introduced into a 250ml conical flask add 100ml of carbon dioxide free water and weigh In the second flask 100ml carbon dioxide free water serve as blank and weigh. Close the two flasks with neutral glass dish or aluminum foil rinsed with carbon dioxide free water. The flask is then placed in on auto clave and maintain the temperature at 121oC for 30minutes and carry out the operations similar to those described in Test A for surface hydrolytic resistance. After cooling remove the closure, wipe the flask and adjust the original weight by adding carbon dioxide free water. Transfer 50ml (corresponding to 10g of glass grains) of the clear supernatant liquid into a conical flask. 50ml of water is taken in other flask which is used as blank 0.1ml methyl red solution is added as indicator and titrated with 0.001M hydrochloric acid until the color of the liquid is same as that obtained with blank. Subs tract the value of the blank and express the result in millilitres of hydrochloric acid consumed per 10g of glass. Type I glass containers require not more than 2.0ml, Type II or III requires not more than 17.0ml and Type IV glass containers requires not more than 30.0ml of 0.001M hydrochloric acid.


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