MDM: Packaging and stability

Question 1

What is drug stability?

Answer 1

The ability of a pharmaceutical dosage form to maintian its physical, chemical and therapeutic properties within the time used by the patient

Question 2

What are chemical instabilities

Answer 2

• oxidation
• hydrolysis
• photodegradation
• temperature
• polymorphic changes
• isomerism

Question 3

What are physical instabilities?

Answer 3

• Water content
• pH
• appearance
• rheology
• SDF - srength of tablet and dissolution
• suspension - redispersability
• Precipitation/ particle size

Question 4

What are examples of other types of instabilities?

Answer 4

• Packaging: absorption, adsorption, leaching
• microbiological
• inncorrect storage/ usage

Question 5

What are processing instabilities in SDFs?

Answer 5

• Oxidation: Movement of particles in mixing and granulation
• Hydrolysis: use of aqueous granulation solvent or humidity of air
• Thermal: heat used for drying granulation or heat used in coating process

Question 6

How can instabilities for SDFs be avoided?

Answer 6

• identify Cause and remove it:

1. Water (hydrolysis) - don’t granulate
2. thermal degradation - remove need for heat
3. air (oxidation) - Do process under N2 blanket
4. Light degradation - find problrmatic wavelength and use light without

Reduce effects:

1. •Add anti-oxidants to formulation
2. •Reduce water content in granulating solution.
3. •Dehumidify the environment
4. •Use lower temperatures (non-aqueous granulation).
5. •Minimise the length of time the materials are handled in the presence of light

Question 7

How to over come hydroylsis in liquid/ semi- solid dosage forms

Answer 7

• Form a complex
• Modify chemical structure
• Solubilise in micelles

Question 8

How to protect Liquids/ semi solids from oxidation

Answer 8

Removal of O2:

• use inert gas to displace air above the product
• boil water immediately before use
• use well filled containers

Protection from light:

• Energy from light fuels oxidation process therefore packaginf methods are used to protect it from light:
• Cartons, light resistant containers

pH control

• Oxidation prodcues H+ ions therefore and acidic envirmoent will help prevent it

Solubilisation:

• Oxygen is less soluble in an oily component than in an aqueous so dissolving the drug in oil to prodcue an emulsion will protect it

Question 9

What other stability issues are there with Liquid/ ss forms? How do you prevent these?

Answer 9

• Manufacture in suitable enviroment
• add preservative to prevent microbial growth
• parabens and phenoxyethanol

Question 10

What packaging instabilities is there?

Answer 10

• Drug not sufficently protected by packaginf or packaging has materials which coulc potenital leach out into product

Question 11

Whar types of stability tests are done?

Answer 11

• Preformulaiton - stress testing done on drug ONLY. Determines potential areas of drug degradation pathways
• Binary mixes - 1:1 ratio of drug and excipents. Tested at high temperatures or using DSC. Can have tertiary mixtures
• Formulation and container development -
• Post authorisation tsudies - supports kucebcubg aookication

Question 12

Talk about expiry dates

Answer 12

All medicinal products have them

• Shelf life - time taken for drug to reduce to 95% of its orginal value
• SS/ liquids have shorter SL
• Powders have 2 SL - 1 dried and 1 reconstitued

Question 13

What are the reasons for packaging?

Answer 13

• Patient loyalty
• Product identity
• protect the product
• patient compliance
• presnetation of the information
• tamper protection and child resistanr

Question 14

What packaging is used for liquids?

Answer 14

• Glass: Good moisture and light protection. Amber or opaque bottles. 3 types of glass
• Plastic: Opaque bottles used. Provides some light protection not as good as metal/ glass. Moisture protection depends on polymer used
• Aluminium: Same moisture protection and better light protection. Internal surfaces need to lacqured to prevent interactions

Question 15

What packaging is used for semi solids?

Answer 15

• Glass bottles: used if materials interact with plastic and for exemperous preperations
• plastic bottles/ jars: see Liquids
• Metal: aluminium. Lacqured internal surface

Question 16

What are additional requirements of bottles?

Answer 16

• Cap
• foil
• Shrink sleeve
• ullage takeup

Question 17

What are the 3 methods of filling liquids/ SS?

Answer 17

• Weight filling: Bottle on tared balance and filled to correct weight
• level filling: Tube filling with another tube at the correct level removing excess
• Volumetric filling: Fixed measuring cylinder or adjustable cylindrical pump

Question 18

What are blow fill sealed techniques used for?

Answer 18

• Expensive or specialised equipment
• parentals
• not suitable for heat sensitive products

Question 19

How are blister packs manufactured?

Answer 19

• Thermoformed - by heat and pressure or vaccum
• Mechanically formed - by pressure to top surface

Question 20

What types of filling is there into blister packs?

Answer 20

• Random filling - moves through hopper into blister pockets
• Guided filling - tubes guide product down into pockets
• pick and place systems - suction pads/ mechanical grippers pick and place into pocket

Question 21

How is intergrity of blister packs measured?

Answer 21

1. Empty blister pack
2. PLaced in coloured liquid
3. pressure applied for set time
4. Check if liquid in pockets
5. repeat with product in blisters

Question 22

What are problems associated with blister packs?

Answer 22

Banana skinning - logitudinal or transverse distortion due to differences in expanaion coefficents of forming and lidding materials

Put in straightening ribs

Question 23

What determines what film is required to cover blister packs? what are they made off?

Answer 23

Depends on level of protection for moisture

aluminium, paper, plastic

Question 24

What quality assesment controls are required?

Answer 24

• Right quantity
• no damage to packaging
• whats on the label is in the packaging
• sterility of product

Question 25

What does the 2nd/ outer packaging provide?

Answer 25

* Patient information * Physical stability during transport of package