Name Reg. no.

Name Reg. no.

Joyanta kundu08103074

Ophthalmic preparations are specialized dosage forms designed to be instilled onto the external surface of the eye, administered inside or adjacent to the eye or used in conjunction with an ophthalmic device.

Ophthalmic products are used: For the treatment of eye diseases. For the relief of symptoms associated with

eye diseases. For diagnosis purposes. As adjuncts ophthalmic surgical procedures.

Ophthalmic products have several types. Such as – eye drops, eye lotions, eye ointments, eye creams, eye gels, contact lens solutions, parenteral products, ophthalmic inserts and powders.

Currently almost all commercially available ophthalmic products are packaged in plastic containers. Obvious advantages-ease of use, less spillage, little breakage- have led to universal acceptance of these plastic packaging components, consisting of bottles, fitment and closures. Alcon was the first company to introduce these packaging components, identified as a “Drop-Tainer” for ophthalmic products, in the late 1940s and saw them adopted by the industry as the standard for packaging topical ophthalmic products.

The plastic bottles for packaging of ophthalmic products are generally made of Low Density Polyethylene(LDPE), either with or without any colorants or with opacifying agents. Polypropylene(PP) or high density polyethylene(HDPE) are also used to meet specific product requirements.

Eye drops(Single-

dose containers):

Plastic bottles(LDPE)

are widely used.

Eye drops(Multiple-dose containers): Traditionally, glass bottles with rubber teat dropper were widely used. Now-a-days, plastic bottles(LDPE) are widely used.

Eye ointments: Flexible plastic

or collapsible metal tubes are

used.

Caps or closures are generally made from Polypropylene(PP) and basically seal the container to prevent contamination or leakage of the product.

Color Pharmaceutical Class

Yellow or Blue Beta-Blockers

Grey Non-Steroids

Pink Steroids

Brown or Tan Anti-Infectives

Orange Carbonic anhydrase inhibitors

Turquoise Prostaglandins

Red Mydriatics

Green Miotics

Plastic containers have sorption and permeability characteristics. Volatile ingredients such as the chlorobutanol and phenylethyl alcohol can migrate into the plastic and eventually permeate through the walls of the container. The sorption and permeation can be detected by stability studies if they are significant. To overcome permeation problems employ a secondary package, such as a peel-apart blister or pouch composed of nonpermeable materials (e.g., aluminum foil or vinyl).

Neutral, Boro-silicate type glass(Type 1 glass) were widely used as a container for ophthalmic preparations, but glass containers are not widely used now which has been replaced by plastic containers(more commonly known as Drop-Tainers).

Parenteral dosage forms differ from all other dosage forms because they are injected directly into body tissue through the primary protective system of the human body, the skin and the mucous membranes. They must be exceptionally pure and free from physical, chemical and biological contaminants. These requirements place a heavy responsibility on the pharmaceutical industry to practice current good manufacturing practices(cGMPs) in the manufacture and packaging of parenteral dosage forms and upon pharmacists and other health care professionals to practice good aceptic practices(GAPs) in dispensing them for administration to patients.

Injectable formulations are packaged into containers made of glass or plastic. Container systems include ampoules, vials, syringes, cartridges, bottles and bags. Ampoules are all glass while bags are all plastic. The other containers can be composed of either glass or plastic and must include rubber materials such as rubber stoppers for vials and bottles, rubber plungers and rubber seals for syringes and cartridges.

• Glass Glass is employed as the container

material of choice for most SVIs. It is composed principally of silicon dioxide, with varying amounts of other oxides such as sodium, potassium, calcium, magnesium, aluminum, boron and iron. Boric oxide will enter into the basic structure of glass formed by silicone oxide and persist as loosely bound, so thereby relatively free to migrate. These migratory oxides may be leached into a solution in contact with the glass.

• According to USP there are four types of glass used as containers. They are- Type 1, neutral, a borosilicate glass Type 2, treated soda lime glass Type 3, regular soda lime glass or soda lime glass of limited alkalinity. Type 4, a soda lime glass not suitable for containers for parenterals. Type 1 glass is suitable for all products as it has the highest resistance to

leachables, permeation and adsorption. It also has a low thermal co-efficient of expansion. Sometimes sulfur dioxide treatment is used for even greater resistance to leachables. Schott has developed a technology called Plasma Impulse Chemical Vapour Deposition(PICVD) that coats the inner surface of of type 1 glass vials with an ultrathin film of silicon dioxide. This film forms a highly efficient diffusion barrier that practically eliminates glass leachables.

Type 2 glass may be suitable for, for example, for a solution that is buffered, has a pH below 7, or it is not reactive with the glass.

Type 3 glass will be suitable principally for anhydrous liquids or dry substances.The glass types are determined by two USP tests. (1)powdered glass test (2)water

attack test . Type 4 is not used for parenteral purpose.

Glass Type

Leaching Extent

Potential Leachables

Permeation Extent

Potential Agents

Adsorption (selective) Extent

Type 1 1 Alkaline earth and heavy metal oxides

0 N/A 2

Type 2 5 Alkaline earth and heavy metal oxides

0 N/A 2

Thermoplastic polymers have been established as packaging materials for sterile preparations such as large-volume parenterals, ophthalmic solutions and increasingly, small-volume parenterals. For such use to be acceptable , a thorough understanding of the characteristics, potential problems and advantages for use must be developed. Three principal problem areas exist in using these materials:

1. Permeation of vapours and other molecules in either direction through the wall of the plastic container.

2. Leaching of constituents from the container to the product.

3. Sorption(absorption and/or adsorption) of drug molecules or ions on the plastic materials.

Permeation, the most extensive problem, may be troublesome by permitting volatile constituents, water or specific drug molecules to migrate through the wall of the container to the outside. This problem have been resolved, for example, by the use of an overwrap in the packaging of IV solutions in PVC bags to prevent the loss of water during storage. Leaching may be a problem when certain constituent in the plastic formulation , such as plasticizers or antioxidants migrate into the product. Sorption may be a problem in selective basis, that is, sorption of a few drug molecules occurs on specific polymers, for example, sorption of insulin and other protien, Vitamin A acetate etc has been shown to occur on PVC bags when these drugs were present as additives in IV admixtures.

A brief summary of some of these compatibility relationships is given below:

Plastic Polymers

Leaching extent

Potential leachables

Permeation extent

Potential agents

Adsorption(selective) extent

LDPE 2 Plasticizers, antioxidants

5 Gases, water vapors.

2

HDPE 1 antioxidants

3 Gases, water vapors.

2

PVC 4 HCl, specially plasticizers.

5 Gases, water vapors.

2

Polyolefins

2 Antioxidants

2 Gases, water vapors.

2

Polypropylene

2 Lubricants

4 Gases, water vapors.

1

PVC large volume IV infusion bag

PVC small volume IV infusion bag

AmpoulesA parenteral product container

made entirely of glass and intended for single use.

The ampoules can be broken at the neck restriction either by scoring or by having a ceramic point (ring or spot) baked on during the manufacture thus causing a weak point. However breaking on the ceramic point can cause colored particles to fall into the product.this led to an alternative where the the ampoule is scored and then has a colored ring above or below the score to indicate the break point( one point cut/open point cut method).

A glass or plastic container closed with a rubber stopper and sealed with an aluminum crimp. Vials are available for single dosing or for multiple dosing. Injection vials can be obtained in either neutral or soda glass and occasionally in treated soda glass.

HDPE Plastic Vials Type 1 Glass Vial for multi dosing purpose

Syringes are devices for injecting, withdrawing or instilling fluids. Syringes consists of a glass or plastic barrel with a tight fitting plunger at one end, a small opening at the other end ac-comodates the head of a needle. Needle Gauge is the outside diameter of the needle shaft; the larger the number, the smaller the diameter. Gauges in common use range from 13 (largest diameter) to 27. Subcutaneous injections usually require a 24-gauge or 25-gauge needle. Intramuscular injections require a needle with a gauge between 19 and 22. Needles between 18 gauge and 20 gauge are commonly used for compounding parenterals.

Disposable plastic syringe Disposable glass syringe

Prefilled Syringe: is a ready-to-use prefilled medication syringe with a needle attached, as with Insulin syringes, Interferon and some emergency drugs. As the pharmaceutical industry continues to seek out drug delivery methods that improve safety and efficiency while reducing costs, the traditional multidose or single-dose vial format for vaccines and injectables is starting to show its age. Developed markets are increasingly turning to packaging vaccines in prefilled, single-use syringes, with more and more companies recognising the benefits that come from this area's innovations. Prefilled syringes have been used to delivery drug categories like vaccines, therapeutic proteins, blood stimulants, erythroproteins and more.

"Syringes made from plastic-based cyclopoly olefin (COP) resin are becoming more common."

Advantages: contamination prevention ease of use and dosages

Cartridges are an ideal packaging for insulin and other drugs. They are used with pen or pump systems, auto injectors and needle free injectors.

The magnetic plungerless injection system is a hand held apparatus with a magnetically driven piston capable of displacing, moving and transferring liquid or gas through a cartridge chamber and into a sterile needle for injections. This apparatus works on the that a magnetic field penetrates glass and plastic walls of the cartridge. A magnet located outside of the cartridge walls and a Ferrous piston positioned inside of the cartridge create strong coupling with the piston repeating the movements of the magnet. Movement of the piston in one direction generates insertion of liquids and movement in the other direction generates extraction.

Rubber based closures are effective in sealing provided there is adequate compression of the rubber. Over compression, disc type seals and relatively shallow stoppers may cause the materials to distort, ruck at the flunge, etc. and thereby causing loss of closure efficiency.

Rubber stoppers are used as closures in IV solutions(ampoules, vials, large volume parenteral containers), cartridge tubes and prefilled syringes.

There are a number of rubbers that may be used in pharmaceutical packing. Butyl rubber and chlorobutyl rubbers have the majority share of parenteral closure market. These materials offer the best resistance to permeation by oxygen and water vapor. Silicone rubbers have limited applications in pharmaceuticals as they are prone to tearing.

Test Basic Principle

Advantages Disadvantages

Acoustic Imaging

Ultrasonic energy focused onto sample submerged in water . Echo patterns produce images.

Visualize delamination

Expensive, Requires experts, not for porous materials.

Bubble test Submerge package in liquid, pressurize and/or temperature cycling to accelerate leakage.

Simple, inexpensive, location of leaks can be observed.

Relatively insensitive.

Test Basic Principle

Advantages Disadvantages

Helium mass spectometry

Helium is placed either inside or outside of the container and migration of helium is detected by mass spectometry.

Inert gas, extremely sensitive test

Expensive, expert personnel is required.

High Voltage Leak Detection(HVLD)

High voltage is applied to sealed container , increase in conductivity correlated to presence of liquid along the seal.

100% automatic inspection, non destructive.Used for ampoules, vials, syringes, blow/fill/seal containers.

Requires liquid fill products.

Tests Basic Principle

Advantages Disadvantages

Residual Gas Ionization Test

High voltage field is applied to vials sealed under vaccum. The field causes residual gas to glow.

Used for Lyophilized products.

Inconsistencies in result.

Liquid Tracer Tests

Packaged immersed in solution of tracer chemical or dye. Pressure/vaccum or temp. cycling used to improve sensitivity. Leakage detected visually or mechanically

Operator independent, inexpensive

Destructive, Large sample numbers need.

1.Remington, The Science and Practice of Pharmacy, 21st Edition, Volume 1, Chapter 41, Page 802-836.

2.MANAGEMENT SCİENCE AND ENGİNEERİNG

Vol. 4, No. 3, 2010, pp. 138-143,www.cscanada.org