1.
classify pleentical packaging system based on the materials used for their
fabrication. Discuss each in bri Enumerate adu, of blister pack and discuss its
components.
Ans
Types of packaging materials used for Glass,Plastics,Rubbers,Paper/card boards,
Metals
Glass has been widely used as a drug packaging material.
Advantages
They are transparent.
They have good protection power.
They can be easily labelled.
Economical
Variety of sizes and shapes
Disadvantages
Glass is fragile so easily broken.
Releas alkali to aqueous preparation
COMPOSITION OF GLASS:
Sand (silicon dioxide) Soda ash (sodium carbonate) Limestone (calcium carbonate) Cullet
(broken glass) aluminium, boron, potassium, magnesium, zinc, barium,
Amber: light yellowish to deep reddish brown, carbon and sulphur or iron and manganese
dioxide
Yellow: Compounds of cadmium and sulphur
Blue: Various shades of blue, cobalt oxide or occasionally copper (cupric) oxide
Green: iron oxide, manganese dioxide and chromium dioxide
PLASTIC:
Plastics may be defined as any group of substances, of natural or synthetic origins,
consisting chiefly of polymers of high molecular weight that can be moulded into a shape or
form by heat and pressure.
TYPES OF PLASTICS
Thermosetting type -
When heated they may become flexible but they do not become liquid
e.g. Urea formaldehyde (UF), Phenol formaldehyde, Melamine formaldehyde (MF), Epoxy
resins (epoxides), Polyurethanes (PURS)
Thermoplastics type-
On heating they are soften to viscous fluid which harden again on cooling.
e.g. Polyethylene (HDPE - LDPE), Polyvinylchloride (PVC), Polystyrene Polypropylene,
Nylon(PA), Polyethylene terepthalate (PET), Polyvinylidene chloride (PVDC), Polycarbonate
Acrylonitrile butadiene styrene(ABS)
Advantages
Less weight than glass,
flexible
Variety of sizes and shapes
Essentially chemically inert, strong, rigid Safety use, high quality, various designs
Extremely resistant to breakage
Disadvantages
Absorption permeable to moisture
Poor printing, thermostatic charge
RUBBER:
Rubber is used mainly for the construction of closure meant for vials, transfusion fluid
bottles, dropping bottles and as washers in many other types of product.
Advantages:
Permeability to water vapour.
Water absorption is very low.
They are relatively cheaper compared to other synthetic rubbers.
Disadvantages:
Slow decomposition takes place above 130 - C.
Oil and solvent resistance is not very good.
i. Nitrile rubber:
Advantages:
Oil resistant due to polar nitrile group. Heat resistant.
Disadvantages:
Absorption of bactericide and leaching of extractives are considerable.
ii. Chloroprene rubbers:
Advantages:
Oil resistant. heat stability is good
iii. Silicon rubbers:
Advantages:
Heat resistance.
Extremely low absorption and permeability of water.
Excellent aging characteristic.
METALS:
Metals are used for construction of containers. The metals commonly used for this purpose
are aluminium,tin plated steel, stainless steel, tin and lead
Advantages:
They are impermeable to light, moisture and gases.
They are made into rigid unbreakable containers by impact extrusion.
They are light in weight compared to glass containers.
Labels can printed directly on to their surface.
Disadvantages:
They are expensive.
They react with certain chemicals
COLLAPSIBLE TUBES METAL
The collapsible metal tube is an attractive container that permits controlled amounts to be
dispensed easily, with good reclosure, and adequate protection of the product.
It is light in weight and unbreakable and lends itself to high speed automatic filling
operations.
Most commonly used are tin, aluminium and lead.
Component
1.Selection of forming film:
Consideration must be given to the;
1. Height and weight of the product,
2. Sharp or pointed edges of the final package,
3. And the impact resistance,
4. Aging, migration, and cost of the film.
Types of forming films are;
1. Thermoforming film Examples are;
Rigid PVC
PVDC (Polyvinylidene chloride)
CTFE (PVC/chlorotrifluoroethylene)
PS (Polystyrene)
2. Cold forming film
Example (ALUMINIUM foil)
2.Lidding Material:
"The lidding material provides the base or mai structural component upon which the final
blister package is built" It must be selected according to;
• The size,Shape,And weight of the product ,As well as the style of the package to be
produced
3.Important consideration in lidding Lidding Material selection are:
• The surface of the lidding material must be compatible with the heat-seal coating process.
Clay coatings are added to the lidding material to enhance printing.
Heat-sealing and printability are both important considerations in blister packaging, and the
lidding material must offer the best workable compromise.
4. Heat seal coating:
"Heat-seal coatings provide a bond between the p blister and the printed lidding material."
"For blister packages, heat-seal coatings are perhaps the most critical component in the
entire system.
These solvent or water based coatings ca applied to rolls or sheets of printed paperboard
using roll coaters, gravure or flexographic methods, knives, silk-screening, or sprays.
Whatever the system, it is essential that the proper coating weight be applied to the lidding
material for optimum heat-sealing results.
5. Hot tack:
"Hot tack is particularly important because the product usually is loaded into the blister and
the lidding material heat sealed in place (face down) onto the blister. When the package is
ejected from the heat-seal jig, the still-warm bond line must support its entire weight.”
"The heat-seal coating must precisely match t lidding material and the plastic material of the
forming films.”
2.Describe various quality control testing of packaging materials for pleentical
products,
Ans
The materials used for fabricating all types of packaging systems may have certain
interactions with formulation components.
In addition, suitability of these materials in terms of ease of administration, storage and
stability over shelf life is of much significance.
Also, both primary packages and shipping containers have a risk of being dropped or being
impacted by other items and in such cases package integrity and product protection are
important packaging functions.
Therefore, quality control tests are performed to measure the resistance of packages and
products to controlled laboratory shock and impact in addition to safety testing.
There are various tests for determination of quality, integrity and compatibility of packaging
materials.
The specification and requirement of quality testing depends on type of pharmaceutical
materials used.
The requirement of packaging material testing is set according to specification of regulatory
agencies like WHO GMP, U.S. FDA and ICH guidelines.
Testing of Packaging Materials
Tests applied to packaging materials are physical, chemical, mechanical and environmental.
i. In physical testing, physical appearance of formulation and packaging components is
tested which should be retained during the shelf life of formulation at specified storage
conditions. A visual appearance change is the first indication of instability. Physical changes
include but are not limited to discoloration, deformation, breakage, leakage, etc. Physical
changes can be easily detected by visual observation or using optical microscopy.
ii.Chemical testing includes pH test, test for chloride and sulphate in case of paper or board,
test for alkalinity of glass, compatibility test with drug and excipients, etc.
iii. Mechanical testing uses standard tests available for the effect of creasing, folding, hot
tack test, tensile test and coefficient of friction.
iv. In environmental testing, materials may be tested for absorption of
*Quality Control Tests for Packaging Materials
(a) Tests for identification:
Identification of raw material quality for packaging components is a prime quality testing
requirement.
Identification test confirms the of packaging components against the specifications. quality
(b) Tests for dimensions:
Every packaging system is manufactured with different components which are assembled
with each other for intended use.
It is important that all dimensions of these components and assembled packaging system
should be within the acceptable limits to perform the respective function during shelf life and
at its intended use.
In case of pediatric oral drops, calibrated droppers are used to avoid compromised efficacy
to avoid underdosing and toxicity in case of overdosing.
(c) Tests for formulation volume in container:
Liquid formulations have a definite fill volume in the packaging system which is generally
aimed to provide the labeled quantity to the
patient in a single dose or in uniformly divided doses.
(d) Tests for deliverable volume/dose:
Each formulation needs to be delivered in the recommended dose by the intended route of
administration. Many pharmacopoeias provide deliverable volume tests for different
formulations. Deliverable volume depends on the packaging components primarily
associated with formulation characteristics such as viscosity and surface tension.
e) Tests for extractable, leachable and delamination:
Primary packaging materials are prepared by using some chemicals such as stabilizers to
provide necessary characteristics as per requirements.
These chemicals may get extracted into the drug formulation. The extractables, or
leachables or delamination causes potential toxicity after administration. Studies need to be
done during the laboratory scale stability batches and/or exhibit batches.
Packaging material plays an important role in keeping the formulation safe and unchanged.
(f) Testing for formulation protection:
A container intended to provide protection from light or offered as a light-resistant container
must meet the requirements of the U.S.P. light transmission test.
The procedure requires the use of a spectrophotometer, with the required sensitivity and
accuracy, adapted for measuring the amount of light transmitted by the plastic materials
used for the container.
(g) Tests for formulation and packaging material compatibility:
A leachability test is performed to evaluate the amount and/or nature of any chemical that
migrate from the plastic material in to the pharmaceutical formulation vehicle for the length of
shelf-life claim. The drug product is evaluated at regular intervals, such as at 1, 3, or 6
months or at 1 or 2 years, until the length of the shelf life claim has been met.
(h) Tests for product safety:
Packaging system components should not leach any harmful or undesirable amounts of
substances into the formulation which a patient will be exposed during treatment.
Determining the safety of a packaging component is not a simple process, and a
standardized approach has not been yet well established. Il establis
(i) Tests for package performance:
Package performance is an important attribute for its suitability to be used as container
closure system for the accurate drug delivery. It depends upon its ability to function in the
manner for which it is designed. The major considerations when evaluating package
performance are its functionality (to improve patient compliance). minimizing waste, or
improving ease of use and delivery of drug in right amount or at right rate.
3.What are the different selection criteria for glass-as packaging material for
injectable products?
Ans
GLASS:
Glass has been widely used as a drug packaging material.
Advantages
They are transparent.
They have good protection power.
They can be easily labelled.
Economical
Variety of sizes and shapes
Disadvantages
Glass is fragile so easily broken.
Release alkali to aqueous preparation
COMPOSITION OF GLASS:
Sand (silicon dioxide) Soda ash (sodium carbonate) Limestone (calcium carbonate) Cullet
(broken glass) aluminium, boron, potassium, magnesium, zinc, barium,
Amber: light yellowish to deep reddish brown, carbon and sulphur or iron and manganese
dioxide
Yellow: Compounds of cadmium and sulphur
Blue: Various shades of blue, cobalt oxide or occasionally copper (cupric) oxide
Green: iron oxide, manganese dioxide and chromium dioxide
MANUFACTURE OF GLASS:
The four basic processes used in the production of glass are:
Blowing uses compressed air form the molten glass in the cavity of metal mold.
In drawing, molten glass is dies or rollers that shape the soft glass. pulled through
In pressing mechanical force is used to press the molten glass against the side of a mold.
Casting uses gravity or centrifugal force to cause molten glass to form in the cavity of mold.
TYPES OF GLASS
Type I-Highly resistant borosilicate glas
Type II-Treated soda lime glass
Type III- Soda lime glass
NP-soda glass (non parenteral usage)
Type I - Borosilicate glass
Alkalinity is removed by using boric oxide to neutralized the oxide of potassium and sodium
It is highly resistant glass.
It has high melting point so can with stand high temperatures.
It is more chemically inert than the soda lime glass
It can resist strong acids, alkalies and all types of solvents. Reduced leaching action.
Uses:
Laboratory glass apparatus.
For injection and water for injection.
Type II-treated soda lime glass
Type II containers are made of commercial soda lime glass that has been dealkalized or
treated to remove surface alkali.
The de-alkalizing process is know as sulphur treatment.
Sulfur treatment neutralizes the alkaline oxides on the surface, rendering the glass more
chemically resistant.
Uses:
Used for alkali sensitive products. Infusion fluids, blood and plasma. Large volume container.
Type III glass-Regular soda-lime glass
This is a type of untreated glass that has average or better-than-average (moderate)
hydrolytic resistance.
This glass is suitable for non-aqueous preparations for parenteral use, powders for
parenteral use (except for freeze dried preparations) and non-parenteral preparations.
Type IV glass-Non-parenteral glass
This is a general purpose soda-lime glass and is not used for parenteral products but for oral
or topical formulations.
Type IV colored glass is used to provide protection to the formulation contents against
ultraviolet rays that prevent photochemical degradations.
4.Write a short note on plastics as a pharmaceutical packaging material.
Ans
Plastics may be defined as any group of substance, of natural or synthetic origins, consisting
chiefly of polymers of high molecular weight, that can be moulded into a shape or form by
heat & pressure.
They usually consist of large molecules of organic materials which are based on certain
building block molecules, undergo a process known as polymerization, a plastic or long
chain polymer is produced.
Other material such as accelerators, initiators, solvents & catalyst can be added during
polymerization to improve the characteristics.Advantages
1.Light weight
2.Reduced volume (warehousing & distribution cost reductioo
3.Good resistance to mould & bacteria.
4.Generally inert chemically, but be wary of "solvents"
5.Usually have good impact strength; difficult to break, if breakage occurs fragments tend to
be less hazardous than glass.
6.Wide design & decorative possibilities.
Disadvantages
1.No plastic is totally impermeable to moisture, gases etc.
2.Most plastics permit some passage of light. Even highly pigmented plastics & those with
UV absorber are likely to let certain wavelengths through.
3.Many are difficult to clean or are liable to attract dust & dirt under unfavorable conditions.
4.May be permeable to, or subject to attack by, organic substances, particularly solvents.
5.Subject to adsorption or absorption according to formulation ingredient.
6.Light weight & thin wall section may require specific production line handling.
7.Fully effective closing systems are sometimes difficult to achieve.
8.Certain designs may show panelling or cavitation
Types of Plastics
1) Thermoplastic Polymers
These are heat softening materials which can be repeatedly made mobile & then reset to a
solid state by cooling.
Under conditions of fabrication they can be moulded by tem re & pressure.
Eg. Polyethylene, PVC, polystyrene, polypropylene, nylon, polyester
2) Thermosetting Polymer
These are polymers produced by a polymerization process involving a curing or vulanisation
stage during which the material becomes 'set' to a permanent state by heat & pressure.
Further heating leads to decomposition of the plastic
5.write in detail about the Regulatory considerations for development of a
pharmaceutical packaging.
Ans
While packaging is important for marketing, pharma packaging is highly regulated.
Packaging materials for pharmaceutical use plays crucial roles in the marketing of
pharmaceutical products in a regulated market.
It is mandatory for packaging materials to comply with respective regulatory
recommendations and guidance.
Regulatory agencies closely monitor the quality of packaging materials used for
pharmaceutical drug products by ensuring the adherence of respective manufacturer's
compliance with cGMP.
Non- compliance guidelines results in compromised drug product quality and subsequently
recall of drug product from respective market. Examples of such cases are the recall of drug
product due to defective container, mis packaged, mislabeled container, etc.
Packaging components of any drug product has the major role of formulation protection. For
example, in case of ophthalmic aqueous solution, semipermeable LDPE containers should
prevent water evaporation during shelf life. Compromised LDPE containers result in
increased drug strength due to reduced volume of ophthalmic solution which may cause
toxicity. Drug products are administered by the users in a required dose and route of
administration. Packaging components also has major impact on product identification, dose
delivery and ease of administration of drug product. For safe administration of drug product,
packaging components should work as per prescribed specifications. Quality of drug product
equally depends on packaging components in contact with the formulation.
The specific U.S. FDA regulation states that "containers, closures and other component
parts of drug packages, to be suitable for their intended use, must not be reactive, additive
or absorptive to the extent that the identity, strength, quality or purity of the drug will be
affected." The packaging material must be approved for such use, along with the drug,
before its marketing.
The drug manufacturer must include data on the container and package components in
contact with the pharmaceutical product in its NDA.If the U.S. FDA determines that the drug
is safe and effective, and that the package is suitable, it approves the drug and package.
It is critical for the packaging scientist to select the correct packaging materials to ensure
stability of the formulation and to remain in compliance with U.S. FDA regulations. The U.S.
FDA expects that every proposed packaging system should be suitable for its intended use.
