Introduction-[Packaging, Labeling, Storage and Stability]

Packaging

An economical means of providing presentation, protection, preservation, identification, information, containment, convenience, and compliance for a drug product.

Immediate Container

Primary Packaging is also known as ____ ?

Primary Packaging

[Primary vs. Secondary Packaging]

Has direct contact with the drug

Primary Packaging

[Primary vs. Secondary Packaging]

• Has a direct effect on the drug.

• Bottle

• cap

• cap liner

Examples of Primary Packaging [3]

Secondary Packaging

[Primary vs. Secondary Packaging]

• External to the primary container.

Secondary Packaging

[Primary vs. Secondary Packaging]

• Adds physical protection and marketing information.

• Cartons

• boxes

• shipping containers

• pallets

Examples of Secondary Packaging [4]

• Well-closed Container

• Tight Container

• Hermetic Container

• Light-resistant Container

Classification of Containers

According to Protection Ability [4]

• Single-unit container

• Multiple-unit container

Classification of Containers

According to Quantity Held [2]

Well-closed Container

[Classification of Containers by Protection Ability]

Protects against extraneous solids and loss of drug under ordinary conditions of handling, shipment, storage, and distribution.

Tight Container

[Classification of Containers by Protection Ability]

Protects from extraneous solids, liquids, or vapors, from loss of drug, and from efflorescence, deliquescence, or evaporation under ordinary conditions of handling, shipment, storage, and distribution.

Hermetic Container

[Classification of Containers by Protection Ability]

Impervious to air or any other gases under ordinary conditions of handling, shipment, storage, and distribution.

sterile

Hermetic Container is generally _____ [unsterile/sterile] ?

Light-Resistant Container

[Classification of Containers by Protection Ability]

Protects the contents from photochemical deterioration.

• Amber

• opaque

• blue glass or plastic.

Examples of Light-Resistant Container [3]

Single-unit Container

[Classification of Containers by Quantity Held]

Designed to hold a quantity of drug intended for administration as a single dose.

Single-unit Container

[Classification of Containers by Quantity Held]

Sterility is not assured after opening.

• Ampule

• prefilled syringe

Example of Single-unit Container [2]

Multiple-unit Container

[Classification of Containers by Quantity Held]

Contains more than a single dose of the medication.

Multiple-unit Container

Vial is an example of ____ [single-unit / multiple-unit container]

Glass

[Materials Used for Packaging]

Available in white flint (clear), amber, or colored types.

Type I

[Type of Glass]

Highly resistant borosilicate glass

Type II

[Type of Glass]

Treated soda lime glass

Type III

[Type of Glass]

Soda lime glass

Type NP

[Type of Glass]

General purpose soda lime glass

• Type I (Highly resistant borosilicate glass)

• Type II (Treated soda lime glass)

• Type III (Soda lime glass)

Type of glass use for parenterals

Type NP (General purpose soda lime glass)

The only type of glass use for other products (except parenterals)

Powdered Glass Test

What is the standard test for the following?

• Type I (Highly resistant borosilicate glass)

• Type III (Soda lime glass)

• Type NP (General purpose soda lime glass)

Water Attack Test

What is the standard test for “Type II (Treated soda lime glass)” ?

Polypropylene (PP)

[Type of Plastic]

Autoclavable

Polyvinyl Chloride (PVC)

[Type of Plastic]

____-

• Rigid and good clarity

• Used for blister packaging

Polyethylene Terephthalate (PET)

[Type of Plastic]

For beverages

• PETG (PET glycol)

• APETG (amorphous PET glycol)

Types of Polyethylene Terephthalate (PET)

PETG (PET glycol)

Type of Polyethylene Terephthalate (PET) :

• Has transparency and luster

PETG (PET glycol)

Type of Polyethylene Terephthalate (PET) :

• Can undergo gamma radiation sterilization

Polyethylene (PE)

[Type of Plastic]

Cannot be autoclaved

Low-density (LDPE)

Type of Polyethylene (PE)

• For droppers and spray

High-density (HDPE)

Type of Polyethylene (PE)

• For solid oral preparations

• Lightweight

• Flexibility

• Resistance to impact

Advantages of Plastic Packaging [3]

• Permeability (external environment to container)

• Leaching (container to content)

• Sorption (internal content to container)

• Transmission of light / Permeation of light

• Alteration of container upon storage

Disadvantages of Plastic Packaging [5]

Permeability

External environment to container

Leaching

Container to content

Sorption

Internal content to container

Transmission of light

The permeation of light

• tin

• aluminum

• aluminum alloy

Example of Metal Materials used for Packaging [3]

• labels

• cartons

• layer boards

Example of Paper and Board Materials used for Packaging [3]

• sachets

• seals

• strips

• blisters

Example of Films, foils and laminations Materials used for Packaging [4]

Rubber

Used as a closure (e.g., a stopper) for sterile products

Cold

[Recommended Storage Conditions for Labeling]

Not exceeding 8°C

Freezer

[Recommended Storage Conditions for Labeling]

A cold place thermostatically controlled between -25°C to -10°C

Refrigerator

[Recommended Storage Conditions for Labeling]

A cold place thermostatically controlled between 2°C to 8°C

Cool

[Recommended Storage Conditions for Labeling]

Any temperature between 8°C to 15°C

Room Temperature

[Recommended Storage Conditions for Labeling]

The temperature prevailing in a working area (usually 20°C to 25°C)

Controlled Room Temperature

[Recommended Storage Conditions for Labeling]

20°C to 25°C, or alternatively 15°C to 30°C (subject to specific product requirements)

Warm

[Recommended Storage Conditions for Labeling]

30°C to 40°C

Excessive Heat

[Recommended Storage Conditions for Labeling]

Above 40°C

True

[Additional Guidelines for Storage Labeling]

True or False:

The use of terms such as “ambient conditions” or “room temperature” is unacceptable.

True

[Additional Guidelines for Storage Labeling]

True or False:

General precautionary statements, such as “Protect from light” and/or “Store in a dry place”, may be included, but should not be used to conceal stability problems

True

[Additional Guidelines for Storage Labeling]

True or False:

If applicable, recommendations should also be made as to the utilization period and storage conditions after opening and dilution or reconstitution of a solution, e.g., an antibiotic injection or suspension supplied as a powder for reconstitution

freezing

[Additional Guidelines for Storage Labeling]

True or False:

Specific requirements should be stated, particularly for drug products that cannot tolerate _____

Stability

Capacity of a drug to remain within its specifications over time.

90% of the labeled potency

Minimum Acceptable Potency Level of a drug is ______ % of the labeled potency. ?

Overage

• The excess medicaments added during the manufacturing of unstable drugs to ensure the potency remains above the minimum level throughout the product's shelf life.

15%

• A _____ % decrease in potency of antibiotics is considered admissible (acceptable) .

• 15%

• 20%

The following Overages normally should not exceed:

_____-% – for dry dosage forms.

_____-% – for fluids.

25%

The following Overages normally should not exceed:

_____%

for

• ointments

• suppositories

• aerosols

• creams

• foams

Real-Time Stability Studies

[Stability Testing Methods]

• Purpose: To evaluate the product under recommended storage conditions for its intended shelf life.

Real-Time Stability Studies

[Stability Testing Methods]

Method: Products are stored under specified conditions (e.g., 25°C and 60% relative humidity for pharmaceuticals) and tested at predetermined intervals.

Real-Time Stability Studies

[Stability Testing Methods]

• Advantages: Provides the most accurate prediction of a product’s shelf life and stability.

Real-Time Stability Studies

[Stability Testing Methods]

• Limitations: Time-consuming, as it requires the full duration of the product’s intended shelf life to complete.

Accelerated Stability Studies

[Stability Testing Methods]

• Purpose: Assess the product's stability under elevated stress conditions to predict its shelf life more quickly.

Accelerated Stability Studies

[Stability Testing Methods]

• Method:

  • - Products are stored at higher temperatures and humidity levels (e.g., 40°C and 75% relative humidity for pharmaceuticals)

  • Tested at shorter intervals.

Accelerated Stability Studies

[Stability Testing Methods]

• Advantages: Provides faster results, helping to identify potential stability issues and reduce time to market.

Accelerated Stability Studies

[Stability Testing Methods]

Limitations:

• May not always accurately predict real-time stability, especially for products sensitive to stress conditions.

• Less accurate than real-time studies.

Forced Degradation Studies

[Stability Testing Methods]

• Purpose: Identify potential degradation pathways and the intrinsic stability of a product by exposing it to extreme conditions.

Forced Degradation Studies

[Stability Testing Methods]

• Method: Products are subjected to severe stress conditions such as high temperatures, strong acids or bases, oxidation, and UV light.

Forced Degradation Studies

[Stability Testing Methods]

• Advantages: Helps to understand degradation mechanisms and develop stability-indicating analytical methods.

Forced Degradation Studies

[Stability Testing Methods]

• Limitations: Conditions may be too harsh and not reflective of normal storage conditions, potentially overestimating degradation rates.

Shelf-Life Extension Studies

[Stability Testing Methods]

• Purpose: Evaluate whether the shelf life of an existing product can be extended beyond its current expiry date.

Shelf-Life Extension Studies

[Stability Testing Methods]

• Method: Products nearing the end of their shelf life are subjected to real-time or accelerated stability studies to determine if they remain within acceptable quality limits.

Shelf-Life Extension Studies

[Stability Testing Methods]

• Advantages: Helps to extend product shelf life, reducing waste and costs.

Shelf-Life Extension Studies

[Stability Testing Methods]

• Limitations: Limited to products already close to their expiry date and may not be applicable for all products.

In-Use Stability Studies

[Stability Testing Methods]

• Purpose: Assess the stability of a product after it has been opened or prepared for use, ensuring it remains effective and safe during its intended usage period.

In-Use Stability Studies

[Stability Testing Methods]

• Method: Products are tested under conditions that simulate actual use, such as repeated opening/closing, exposure to air, or reconstitution in a solvent.

In-Use Stability Studies

[Stability Testing Methods]

• Advantages: Ensures product stability and safety throughout its usage period, providing crucial information for end users.

In-Use Stability Studies

[Stability Testing Methods]

• Limitations:

  • Specific to the intended use conditions

  • may not apply to unopened products.

Temperature

[Key Factors Affecting Stability]

Accelerates chemical reactions (degradation) and causes physical changes (crystallization, separation).

High temperatures

[Key Factors Affecting Stability]

_____- [High / Low] temperatures can cause hydrolysis, oxidation, and degradation of proteins, which can result in loss of potency and formation of toxic impurities.

• hydrolysis

• oxidation

• degradation

[Key Factors Affecting Stability]

High temperatures can cause _______ [3] of proteins, which can result in loss of potency and formation of toxic impurities

Low temperatures

[Key Factors Affecting Stability]

________- [High / Low] temperatures can cause crystallization, precipitation, and physical instability.

• crystallization

• precipitation

• physical instability

[Key Factors Affecting Stability]

Low temperatures can cause _____ [3]

Humidity

[Key Factors Affecting Stability]

Can cause hydrolysis, microbial growth, caking, or loss of volatile components, especially in solid dosage forms.

Photolysis

[Key Factors Affecting Stability]

Can cause photochemical reactions, such as oxidation, isomerization, and degradation, which can affect drug stability.

• oxidation

• isomerization

• degradation

[Key Factors Affecting Stability]

Photolysis Can cause photochemical reactions, such as_______ [3], which can affect drug stability.

drug stability

[Key Factors Affecting Stability]

Photolysis can cause photochemical reactions, such as oxidation, isomerization, and degradation, which can affect ______ ?

pH

[Key Factors Affecting Stability]

Affects drug solubility and degradation rates, as acids/bases can catalyze hydrolysis and other reactions.

acids/bases

They can catalyze hydrolysis and other reactions.

Excipients & Formulation

[Key Factors Affecting Stability]

Compatibility between the drug and inactive ingredients (excipients) is crucial; some interactions can accelerate degradation.