Formulation & Processing Flashcards
Typical Autoclave Cycles for :-
a) Steam
b) Dry Heat
a) 121’C 15 mins or 134’C for 35mins
b) 160’C 2hrs or 170’C 30mins
How do we ensure reliability of autoclaves?
Daily - Bowie Dick
Weekly - Leak Testing
Annually- Re-qualification- leak rate, air detector, Bowie dick, Automatic Process Control Testing, Load Testing (Min / Max), BI testing
What are the considerations for autoclave validation?
Define Process - Cycle temperature and duration (121’C 15mins), F0 cycle min SAL 10-6, what is the formulation?, Load Configuration (Max / Min)
Equipment- Validation/Qualification, Calibration- air detector, pressure gauges, leak test rate, steam quality, Empty Chamber Studied (Hot /Cold) spots
Heat Penetration
BI Study - Geobacillus Sterothermophilus
What are the different types of Leak testing for sterile products?
Camera Systems
Vacuum Decay
Helium Leak Test
Dye Ingress Test
Bubble Test
High Voltage Application
What is the minimum batch size for PST’s?
5000
Give examples of activities carried out in:-
Grade A
Grade B
Grade C
Grade D
A - Aseptic Processing / High risk filling Operations
B - Background to filling in Aseptic preparations.
C - Preparation of solutions to be filtered and some preparations for terminally sterilised products.
D - Handling of components after washing, preparation of solutions for terminal sterilisation.
What testing would you do to qualify a clean room?
Particulate Counts
Airflow Volume & Velocity
Differential Pressures
Filter Integrity Testing
Airflow Visualisation
Recovery Testing
EM Monitoring
Containment leakage
How do we validate filters?
Bacterial Challenge Testing
- Bravundimonas diminuta
- Concentration of 107 organisms per cm2
-Direct inoculation of your product is preferred (not always possible)
- Worst Case conditions - eg max pressure time and temp.
Routine test for inhalation products?
Appearance
Weight of Container
Leak Rate
Spray Pattern
Water Content
Valve Delivery
Related Substances
Dose content uniformity
Particulates
Micro
What is the temperature for disintegration of tablets?
35-40 degrees Celsius (body temp)
Common Problems with tablets:-
Capping - air trapped in mix during compression , poor flow - uneven distribution of material
Lamination- over compression , air trapped,
Cracking- large granules or granules to dry
Hardness variation- unusual size or distribution of granules
Sticking - excessive moisture or improper lubrication , tooling issues, inadequate dwell time during compression
Mottling - improper mixing or coating issue , insufficient drying so moisture trapped
Flashing - unwanted edge around tablets caused by excess material in due cavity, upper and lower punches are misaligned
Chipping - lack of hardness, high friability, poor tablet design, excessive pressure
What are the components of a tablet and what do they do?
Binding Agent - (Starch) - holds or draws material together
Disintigrant- (croscarmellous sodium) facilitates disintegration after administration
Diluent- (Sorbitol) improves cohesion and compression
Lubricant (Mg Sterate) stops tablet sticking in dies
Glidant- improves powder flow during tablet manufacture
Typical Tablet Specification
Appearance
Average Weight
Friability
Hardness
Assay
Uniformity of Dose
Related Substances
Disintegration
Dissolution
TVAC Yeasts/Moulds
What are the constituents of Nolvadex?
Active - Tamoxifen
Diluent - Lactose Monohydrate
Binder - Maize Starch / Gelatin
Disintigrant - Crosscarmellous Sodium
Lubricant - Mg Sterate
Purified Water - Granulation Fluid
Outline a typical tablet manufacturing process:-
Dispensing > Mixing (API / Excipients Dry) > Granulation (Fluid Addition) > Drying > Sieving/Milling > Blending > Compression > Coating
