Thursday, November 21, 2024

Plastic Containers for Pharmaceutical Use

by | May 16, 2021 2

Plastic packaging systems define a set of packaging materials that are composed wholly or in substantial portion of plastic materials which contain or is intended to contain pharmaceutical formulations. They are very commonly used as packaging materials for most types of pharmaceutical dosage forms due to the several advantages they possess over glass containers.

Because plastic container is, or may be, in direct contact with the pharmaceutical formulations, they are usually made of materials which do not include in their composition any substance that can alter the efficacy or stability of the formulation, or present a risk of toxicity. This article mainly focused on plastic containers, their uses and compositions, types, ideal properties, formation/ moulding techniques, evaluation studies, advantages and disadvantages.

What are plastics?

The term “plastic” is a general common term used to describe a group of non-metallic substances, of natural, semi-synthetic or synthetic origins, consisting chiefly of one or more organic compounds (polymer) of high molecular weight, which can be moulded into the desired shapes and hardened for use when subjected to heat or pressure, with or without the addition of some additives. Plastics constitute about 20 % of weight of all pharmaceutical packaging. They are used for many different types of packs including

  • rigid bottles which serve as packaging systems for solid dosage forms (tablets and capsules)
  • sterile plastic packaging systems for human blood and blood components
  • plastic packaging systems for aqueous solutions
  • bags for parenteral solutions
  • infusion dry powder and metered-dose inhalers
  • squeezable bottles for eye drops, ear drops and nasal sprays
  • jars
  • prefillable syringes
  • flexible tubes
  • sachets, blister packs and strip packs
  • cartridges, nebulizers, and vials etc.

Composition of Plastic Containers

Basically, plastics containers consist of organic materials whose molecules have high molar masses and are composed of a large number of repeating relatively small units referred to as monomers. When these monomers undergo a process known as polymerization, a plastic or a sequentially joined long chain of polymer is formed. This process of polymerization may involve various chemicals which assist the process, such as accelerators, initiators, solvents and catalysts, and as a result, are present in small degree in the plastic formed. These, if found in the plastic after polymerization are generally referred to as process residues.

Plastics may also incorporate processing aids e.g., styrenes, acrylics, calcium carbonates, lubricants, silicone oil etc., which are usually added to assist a process and additives (e.g., plasticizers, colouring matter, fillers/extenders, light stabilizers, reinforcement etc.,) which modify the plastic chemically or physically in some way. Most plastics derive their names from the type of polymer(s) used during manufacture. Virtually any desired property or characteristics can be achieved during plastic formation by proper manipulation of the properties of the polymer(s) and additives used.

Qualities of an ideal plastic container

While selecting a plastic container for a pharmaceutical formulation, it is necessary to know the full manufacturing formula of the plastic, including all additives used during the manufacturing process. This is to enables the formulation scientist assess and eliminate potential hazards, thus making sure that the packaging system is suitable for its intended use. Plastic containers used in pharmaceutical industries should be such that:

  1. The ingredients of the formulation in contact with the plastic package are not significantly adsorbed on its surface or absorbed significantly into or through the plastic container.
  2. The plastic package does not have any effect on the stability of the formulation through the release substances (leaching of plastic materials) in sufficient quantities into the formulation.

Types of plastic packaging system

Plastic packaging system can broadly be divided into two categories: thermoplastics (thermosoftening plastics) and thermosets (thermosetting plastics).

a. Thermoplastics (Thermosoftening plastics)

These are heat softening materials which are usually rigid at operating temperatures but can be remelted and remoulded when exposed to high temperature and pressure. When frozen, however, thermoplastics become glass-like and subject to fracture. Examples of thermoplastics include but are not limited to the five most economical plastics – polyvinylchloride, polystyrene, polypropylenes, polyethylenes, and polyester. Others include nylon, polyvinylidene chloride, polycarbonate etc., Thermoplastics may be further classified into homopolymers which involves one type of monomers, e.g., ethylene polymerized to polyethylene, and copolymers, terpolymers etc., which involve two or more monomers of different chemical substances.

b. Thermosets (Thermosetting plastics)

They are called thermosets because they get distinctly infusible or insoluble when exposed to high temperature/ heat, and thus cannot be remelted and remoulded after their initial heat forming. They are produced by polymerization process involving a curing or vulcanization stage during which the materials become ‘set’ to a permanent state by heat and pressure. Further heating leads to the decomposition of the plastic. Thermosets usually contain additional additives (fillers and reinforcing agents) to obtain best quality. These materials are used as packaging material when good dimensional and heat stability are required. Examples of thermoset resins include phenol formaldehyde (originally known as bakelite), urea formaldehyde, melamine formaldehyde, epoxy resins (expoxies), and certain polyesters and polyurethanes.  These materials are commonly used in the pharmaceutical industry as closures for glass and/or plastic containers, small cases as one time used for methanol cones, protective lacquers and enamels as applied internally and externally to metal containers and a range of adhesive systems.

Differences between thermoplastics and thermosets

  1. Thermoplastics are generally soft, weak, less brittle and more pliable than thermosets which tend to be hard, strong, and brittle.
  2. Thermoplastic melts must be cooled down after processing, for it to solidify, whereas thermosets usually turn into a solid after it has been chemically and thermally activated to form a cross-linked network, a process which is referred to as curing.
  3. Thermoplastics have linear and branched polymeric chains joined by weak van der Waal interactions between monomer chains, whereas thermosets have three-dimensional lattice networks where branches are linked to the main chain by strong covalent bonds.
  4. The average molecular weight of thermoplastics can be defined, whereas that of thermosets is undefined.
  5. Thermoplastics can be easily softened and remoulded when exposed to high temperature and pressure, whereas thermoset cannot be softened and remoulded on exposure to high temperature and pressure.
  6. Thermoplastics are soluble in organic solvents whereas thermosets are insoluble in organic solvents.

Plastic forming processes/ plastic moulding techniques

Various techniques have been employed during manufacture of plastic packaging systems each depending on the type of polymer used and the type of plastic to be formed. Plastic forming processes as described in this write up are broadly divided into thermoplastic processing techniques and thermoset processing techniques.

A. Thermoplastics processing techniques

i. Injection moulding

In this technique, melted plastics are forced into a mould cavity through a long chamber with a reciprocating screw. When cooled, the plastic solidifies and the finished product is ejected from the mould. This technique is mostly used to mass produce plastics articles e.g., syringes, drug inhalation units, bottle caps/closures etc. Materials used in this process include Polypropylene (PP), Acrylonitrile-Butadiene-Styrene (ABS), polycarbonate (PC), nylon and polystyrene.

ii. Blow moulding

This method is often used when the plastic item to be created needs to be hollow. The process is of three types – injection blow moulding, injection-stretch blow moulding and extrusion blow moulding.

a. Injection blow moulding

In this process, molten plastics are injected into a mould to form a plastic tube/ core pin called parison. The plastic tube is then made to conform to the interior design of the blow mould by forcing compressed air through it. This is then followed by the cooling and ejection of the newly formed bottle. Injection blow moulding is ideal for the production of wide and narrow-mouthed plastic bottles, jars, tubes etc. Materials used include Polyvinyl chloride (PVC), Polypropylene (PP), Polyethylene – Terephthalate (PET), Polyethylene (High Density) HDPE), Polyethylene (Low Density) LDPE (LLDPE).

b. injection- stretch blow moulding

In this process, hot liquid plastic is injected into a mould to form a preform. The preform is then stretched while simultaneously being inflated to the desired final shape using compressed air. The newly formed transparent bottle is then ejected from the mould. The above steps can be accomplished either by using the single-stage process or the two-stage process. An injection- stretch blow moulding is said to be a single-stage process if both the preform manufacture and bottle blowing step are performed in the same machine. In the two-stage process, preforms are manufactured, packaged, stored or even sold before being fed later into a reheat stretch blow moulding machine to form a bottle. The most widely used material for injection-stretch blow moulding is polyethylene-terephthalate (PET). Injection stretch blow moulding is used for the production of high quality and very high clarity bottles e.g., Carbonated and soft drink bottles, Health and oral hygiene products, Cooking oil containers, Agrochemical containers and Bathroom and toiletry products.

c. Extrusion Blow Moulding

In this process, the melted polymer is led through a right angle into the annular die. A plunger pushes the melt into an open mould cavity, forming a hollow (usually circular) pipe section/ preform called a parison. The mould then closes, sealing the bottom of the parison and at the same time forming the neck of the bottle. Compressed air is then blown into the parison, forcing it against the inside of the mould. The bottle is then cooled and ejected from the mould. Products produced using this plastic forming process include automotive fuel tanks, watering cans and boat fenders, bottles and containers, venting ducts etc. Polymeric materials used in extrusion blow moulding include Polypropylene (PP), Polyethylene – Terephthalate (PET), Polyethylene (PE)and Polyvinyl chloride (PVC).

iii. Thermoforming process

In this plastic moulding process, thermoplastic sheets/ pre-extruded rigid plastic sheets are horizontally heated to a pliable forming temperature. The preheated sheet is the made to conform to the shape of a mould by stretching it into or unto a mould after which it is cooled and trimmed to a finished shape. Materials that are commonly used in the process include High-Density Polyethylene (HDPE), High Impact Polystyrene (HIPS), Glycolized Polyethylene Terephthalate, Polycarbonates, Acrylonitrile Butadiene Styrene (ABS) etc. Plastic materials manufactured using this process includes cups, lids and plates, trays, blister package, medical device housing etc.

iv. Rotational moulding/ Rotamoulding/ Rotomoulding

In this process, the mould containing the raw material is rotated inside an oven, thus causing the powder to melt and stick to the insides of the mould. The mould is then subjected to cooling using fan and water sprinklers while still maintaining the biaxial rotation. The formed product is then removed from the mould. This process differs from other plastic forming processes in that no external pressure is applied during forming processes. Polymeric materials used in this process include nylon, polyethylene, polypropylene, polycarbonate, PVC etc.  Products like containers, tanks, canoes, and playground slides are made using this technique.

v. Profiles Extrusion

In this process, the plastic raw materials are melted and at the same time traversed along by the action of heated rotary screws. The molten plastic is continuously pushed through a hollow die to create a specific profile shape and thickness. A water bath or spray chamber then cools the extruded and often provide pressure into a vacuum to properly size the product as it passes through. The solid product is then conveyed to take-off rollers that actually pull the softened plastic from the die.   A cutter or saw then creates the final product length. This process is widely used in the manufacturing long lengths of plastic product e.g., medical tubing (Blood drip tubes, catheter tubes), rainfall pipes, gas pipes etc. Typical materials used include High-Density Polyethylene (HDPE), butyrate, Glycolized Polyethylene Terephthalate, Polycarbonates, Acrylonitrile Butadiene Styrene (ABS) etc.

vi. Blown Film

In the blown extrusion process, a very thin die opening which is often fed by multiple extruders faces upward in a round shape. A tall tin bubble is produced vertically by this process and it is cooled as it flows upward. It is then folded and brought down and placed unto rolls or converted into popular film products. Polyethylenes (HDPE, LDPE and LLDPE) are the most commonly used materials for this process. But a wide variety of other materials e.g., Polypropylene, polyamide and Ethylene Vinyl Alcohol copolymer (EVOH) can be used as blends. Materials manufactured using this process include Industry packaging materials (e.g., shrink stretch film, container liners), Consumer packaging materials (e.g. packaging bags, fill and seal packaging film), Barrier film, films for the packaging of medical products etc.

B. Thermoset processing techniques

i. Compression moulding

In this method, the raw material (granules or a slug of preheated plastic) is placed between two heated mould halves. By applying pressure on the preheated mould, the plastic flows and fills the cavity. The parts formed are then air-cooled.  Excess material may leak out from the parting lines during compression to form a flash. Common materials used include  Polyester, Polyimide (PI), Polyamide-imide (PAI), Polyphenylene Sulfide (PPS),  Polyetheretherketone (PEEK), Fiber reinforced plastics etc. Materials formed using this process include electronic device cases, electrical parts, flatware, gears, buttons, buckles, handles etc.

ii. Transfer moulding

In this process, a pre-determined weight of the polymeric raw material is preheated and loaded into a holding champer (pot). Using a hydraulic plunger, the material is then forced/ pushed into a preheated mould cavity through a channel called sprue. The product is held under heat pressure until the material is cured and solidifies. This method has found use in the manufacturing of dishes, handles for cooking pots, some rubber parts like shoe soles, housing for high-voltage switches etc. Although transfer moulding can also be used for thermoplastics, the majority of the materials used in this process are still thermosets, Some of the common polymers used in transfer moulding include Epoxy, Silicone rubber, Phenol-formaldehyde Plastic, unsaturated polyester.

Evaluation studies on plastic containers

  1. Biological Reactivity
  2. Physiochemical Tests
    1. Water extraction
    2. Absorbance
    3. Acidity or alkalinity – this test is carried out only when packaging systems are intended to contain a liquid formulation or a formulation that is dissolved in its container before use.
    4. Organic extractables – total organic carbon.

Advantages of plastic containers

  1. Plastic containers are not breakable.
  2. They are light in weight and resistant to leakage.
  3. They are cheap to manufacture
  4. They can be easily moulded or remoulded
  5. They have excellent finishing
  6. Plastic containers are chemically inert and resistant to corrosion
  7. They are collapsible

Disadvantages of plastic containers

  1. Plastic containers have poor physical stability due to adsorption, absorption lightness and/or interactions between the formulation and the container
  2. They have low heat resistant and poor ductility.
  3. Most plastic containers are usually not as clear as glass, and, therefore, inspection of the contents is impeded.

References

Related keywords: disadvantages of plastic containers in pharmacy, plastic containers for pharmaceutical packaging, pharmaceutical plastic bottles manufacturers, pharmaceutical packaging slideshare, plastic in pharmaceutical industry, 4 disadvantages of plastic packaging, advantages and disadvantages of pharmaceutical packaging materials, function of pharmaceutical packaging.



Comments2

  1. Moses says:

    I like this

Leave a Reply

Your email address will not be published. Required fields are marked *

x