In the pharmaceutical industry it is vital that thepackage selected adequately preserve theintegrity of the product.The selection of a package therefore beginswith a determination of the product’s physicaland chemical characteristics, its protectiveneeds and its marketing requirements.
The material selected must have the following characteristics They must protect the preparation from environmental conditions Must not reactive with the product Must not impart odor/taste to the product Must be non-toxic Must be FDA approved Must meet tamper-resistance requirements
Glass containers Glass is commonly used in pharmaceutical industry because it possesses superior protective qualities, economical and containers are readily available in variety of sizes and shapes Chemically inert, impermeable and with proper closure system it provides excellent barrier protection except light (amber color can give protection against light). Disadvantage: its fragility and weight.
Composition of glass: glass is composed principally of sand, soda ash, lime stone, alumina and cullet. The sand is almost pure silica, the soda ash is sodium carbonate and lime stone, calcium carbonate. The cullet is broken glass that is mixed with the batch and acts as fusion agent for the entire mixture. Reduction in the proportion of sodium ion makes glass chemically resistant.
However without sodium, glass is difficult, expensive to melt. Boron oxide is incorporated mainly to aid in the melting process through reduction of the temperature required. Lead gives the clarity. Alumina to increase the hardness and resistance to chemical action.
Colored glass 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. USP specification for light resistant container requires the glass to provide protection against 290-450nm of light. Amber color meets these above specifications but iron oxide added to produce this color, leach in to the product.
Glass for drugs USP describes the various types of glass and provide the powder glass and water attack tests for evaluating the chemical resistance of glass. The test results are measures of the amount of alkaline constituents leached from the glass by purified water under autoclave temperature conditions. Powder glass test is performed on glass particles and water glass test is performed on whole
The water attack test is used only with type II glass that has been exposed to SO2 fumes under controlled conditions to remove the surface alkali, thereby rendering the glass more resistant chemically. However this resistance is lost if the container is subjected to repeated autoclaving, hot air sterilization
Plastic container Plastic in packaging have proved useful for a number of reasons including the ease with which they can be formed, their high quality and freedom of design. Plastic containers are extremely resistant to breakage and thus offer safety to consumers along with reduction in weight and breakage losses. Plastic containers for pharmaceutical products are primarily made from the following polymers
The principle ingredients of the various plastic materials used for containers is the thermoplastic polymer along with substantial amount of plasticizer, fillers, antioxidants etc. these ingredients are not usually chemically bounded in the formulation and therefore may migrate out of the plastic and in to the product.
Thermoplastic polymers melt at elevated temperature. All plastic materials listed in the table except low density polyethylene and polystyrene can be autoclaved but almost all softens at autoclaving temperatures..
Polypropylene and the copolymer polyethylene-polypropylene is most widely used in parenteral because high melting point 165 0C, low permeability to gases and water vapor. It is translucent. It will withstand autoclaving temperature. Flexiblepolyethylene containers are used for ophthalmic solutions and flexible PVC bags for intravenous solutions
The density of the plastic material directly determines the four basic physical characteristics Stiffness Moisture Stress cracking Gas As the density increases the material becomes stiffer, has higher melting temperature, become less permeable to gases and vapor and become less resistant to stress cracking.
Polytetraphthalate (PET): PET is a condensation polymer typically formed by reaction of tetraphthalic acid. Its excellent impact strength, gas barrier make it attractive for use in cosmetics and mouth washes as well as in other products.
Drug – Plastic considerations A packaging system must protect the drug without in any way altering the composition of the product until the last dose is removed and or till the expiry date of the product .
Drug plastic considerations have been divided in to separate categories Permeation Leaching Sorption Chemical reaction Alteration in the physical properties of plastic or products.
Permeation:- The transmission of gases, vapor or liquids through plastic packaging materials can have an adverse effect on the shelf life of a drug. Permeation of water vapor and oxygen through the plastic wall in to the drug can present a problem if the dosage form is sensitive to hydrolysis and oxidation. Temperature and humidity are important factors influencing the permeability of oxygen and water through plastic. An increase in the temperature reflects an increase in the permeability of the gas.
Material such as nylon which is hydrophilic in nature is a poor barrier to water vapor. The formulations containing volatile ingredients might change when stored in plastic containers
Leaching:- since most plastic containers have one or more ingredients added in small quantity to stabilize or impart a specific property to the plastic, the prospect of leaching or migration from the container to the drug product is present problems may arise with plastics when coloring agent in relatively small quantities are added to the formula. Release of a constituent from the plastic container may leads to drug contamination and necessitate removal of the product from the market.
Sorption:- this process involves the removal of constituents from the drug product by the packaging material. Sorption may lead to serious consequences for drug preparation in which important ingredients are in solution. Since the drug substances of high potency are administered in small doses, losses due to sorption may significantly affect the therapeutic efficacy of the preparation.
A problem commonly encountered in practiceis the loss of preservatives from theformulation. These agents exert their activityat low concentration their loss through thesorption leave the product unprotected againstmicrobial growth.
Chemical reactivity:- certain ingredients that are used in plastic formulation may react chemically with one or more components of a drug product and subsequently alter the appearance of plastic or drug product.
Modification:-the physical and chemical alterations of the packaging material by the drug product is called modification. Deformation in polyethylene containers is often caused by permeation of gases and vapor from the environment or by loss of contents through the container walls.
Some solvent systems have been found to be responsible for considerable change in the mechanical properties of plastic. Oils for example have softening effect on polyethylene. Changes in the polyethylene caused by some surface active agents have been noted. Fluorinated hydrocarbon attack polyethylene and PVC
Quality control tests for plastic containers Containers for Non-injectables: Leakage test: Hold the pack under the water, apply the vacuum and observe for leakage. Clarity test: washed portion of the sample, add 250ml of distilled water, autoclave at 121oc for 30 minutes. The absorbance at 640 nm should be 0.37 to 0.43.
Non volatile residue: evaporate 100ml of the extract obtained in the test for clarity of aqueous extract to dryness and dry to constant weight at 105oc. the residue weight not more than 12.5 mg.
Containers for injectables: In addition to the above tests Water vapor permeability:5 containers filled to nominal volume, wt accurately and allow to stand for 14 days with relative humidity 60% and temperature 20-25oc. reweigh the containers. The loss in weight in each container should not be more than 0.2%.
Collapsible tubes Metal: - Thecollapsible metal tube is an attractive container that permits controlled amounts to be dispensed easily, with good reclosure and adequate protection of the product. The risk of contamination of the portion remaining in the tube is minimal because the tube does not suck back. It is light weight and unbreakable.
Tubes of tin, aluminum and lead are most commonly used. Laminates of tin coated lead provides the appearance and oxidation resistance. Aluminum hardens in use causing tubes to develop leaks.
Tin containers are preferred for food, pharmaceuticals because it is inert and compatible with a wide range of products. Lining: - if the product is not compatible with bare metal, the interior can be flushed with wax type formulations or with resin solutions. A tube with epoxy lining cost 25% more than the same tube uncoated.
Plastic:-Plastic tubes have a number of practical advantages over other containers they are low in cost, light wt, flexible, odorless and inert, unbreakable, they have a unique suck-back features which prevents product ooze. but this feature has a disadvantage of fear for contamination. The most common material currently employed in plastic tubes are low and high density polyethylene.
Laminations Permeation problem associated with plastic tubes and corrosion problems with metal tubes have lead to the emergence of a third type of collapsible tube, the laminated tube. This tube constructed of a lamination containing several layers of plastic, paper and foil. This lamination is welded in to a continuous tube by heat sealing the edges of the lamination together in a machine called sideseamer. The tube is cut in to length and the head is molded on to the tube.
Closures Effective closure must prevent the contents from escaping and allow no substance to enter the container. In evaluating an effective closure system the major considerations are the type of container, the physical and chemical properties of the product and the stability-compatibility requirements for a given period under certain conditions .
closures are available in screw on, thread or lug crimp-on (crown) press-on (snap) Roll-on and Pilfer proof roll-on
Thread screw cap: when the screw cap is applied, its thread engages with the corresponding threads molded on the neck of the bottle. A liner in a cap, pressed against the opening of the container, seals the product in the container. The screw cap is commonly made of metal or plastics.
Lug cap: the lug cap is similar to the thread screw cap and operates on the same principle but it is an interrupted thread on the glass finish, instead of a continuous thread
Crown cap: This style of cap is commonly used as crimped closure for beverage bottle and has remained unchanged for more than 50 years. Press-on:- the cap is applied by application of pressure from the top.
aluminium Roll-on and rolled on pilfer proof metal caps consists of a plain metal shell containing a wadding or flowed-in system, which is placed over the container neck and top pressure applied to give a good impression on the wad. While the pressure is still held, the threads are formed by mechanical inward pressure. In case of pilfer proof closure an additional perforated collar is rolled under a lower bead.
Tamper-resistant packaging As defined by FDA a temper resistant package is one having an indicator or barrier to the entry which if breached or missing, can reasonably be expected to provide visible evidence to consumers that tempering has occurred.
Tamper resistant packing may involve immediate container/ closure system or secondary container closure systems or any combination thereof intended to provide a visual indication of integrity when handled in a reasonable manner during manufacturing, distribution and retail display.
The following package configuration have been identified by FDA as examples of packaging systems that are capable of meeting the requirements of temper resistant packaging. Blister package Strip package Bubble pack Shrink banding Bottle seal Tape seal Breakable caps Sealed tubes Aerosol container
Blister package The blister package is formed by heat softening a sheet of thermoplastic and vacuum drawing the softened sheet in to a mould. After cooling the sheet is released from the mould and proceeds to the filling station of the packaging machine.
The semi rigid tray previously formed is filled with the tablets/ capsules and lidded with a heat sealable backing material. The backing material is usually heat seal coated aluminium foil. The plastic material used includes PVC, PVC/ polyethylene combination. For added moisture protection polyvinylidene fluoride
(saran) or polychlorotrifluoroethylene (aclar) films may be laminated to PVC. The moisture barrier of PVC/ Aclar is superior to that of saran coated PVC. Advantages:-Unit dosing, convenience, child-resistant, pleasing appearance, tamper-resistant
Strip package Strip package is a form of unit dose packaging that is commonly used for the packaging of tablets and capsules. A strip package is formed by feeding two webs of a heat sealable flexible film through a heated crimping roller.
The product is dropped in to the pocket formed prior to forming the final set of seals. a number of different packaging materials are used for strip packaging. For high barrier applications a paper/polyethylene/foil/polyethyle ne laminations commonly used.
Bubble pack The bubble pack can be made in several ways but is usually formed by sandwiching the product between a thermoplastic film and a rigid backing material similar to as in the blister.
Shrink banding The shrink band concept makes use of the heat shrinking characteristics of a stretch oriented polymer usually PVC. The heat shrinkable polymer-PVC is manufactured as a tube in a diameter slightly larger than the cap and neck ring of the bottle to be sealed.
Thisis then placed over the bottle cap and the package is passed through a heated tunnel, which shrinks the plastic cover around the cap, preventing the disengagement of the cap without destroying the shrink band.