Non Steriles Flashcards
What release tests are in place for PMDIs?
Micro
Particle size distribution
Ejection force
Dose delivery
Appearance
Impurities
ID (drug, propellant, adjuvants)
Fill weight
Moisture content
What manufacturing requirements are in place for PMDIs
Minimum grade D
100% checkweigh
0.2u filtration for all liquids
Particle size control
Microbiological control
When are dedicated facilities required
Can’t control risk
Can’t justify risk
Don’t understand risk from tox perspective
part 3 documents in eudralex
EMA guidance for HBEL
Chapter 5- organisational risks and technical risks.
Products requiring dedicated facilities
- sensitising antibiotics
- High potency cytotoxics
- Hormone/steroids
- Radioisotopes
-narcotics
Describe a typical Oral solid dose manufacturing process. What are the CPPs?
What are IPCs?
Dispense/Weigh- Weight for each excipient/Active
Dry blend- Time, Speed, Temp
Granulate- Time, Speed, Shear resistance, Temp, Water quality
Dry- Time temp, Endpoint temp delta or NIR
Micronize- Time, speed, sieve size
Blend- Time, speed
Compress- Fill weight/volume, pre-compression force, compression force, speed.
Coat- Coater speed, gun distance from bed, water quality, agitation speed of bulk solution, temperature, atomisation pressure.
IPCs
Granulate- micro
Drying- Moisture content
Compression- Weight, hardness, thickness, friability, disintegration.
Coating- Appearance vs AQL (ISO 2859)
Can you provide examples of typical excipients in an oral solid dose tablet?
What is in Nolvadex?
Filler- Lactose/Sucrose
Binder- Gelatin, Methyl Cellulose
Disintegrant- Crosspovidone, SSG
Glidant- Silicone dioxide
Lubricant- magnesium stearate
Nolvadex;
Active- Tamoxifen citrate
Diluent- Lactose
Binder- Gelatin/Starch
Disintegrant- Crosscarmellose
Lubricant- Mag stearate
Water- PW
Coating- Hypromellose (Film), Macrgol (plasticiser), Titanium dioxide, PW
Can you describe a typical oral liquids process?
What are the CPPs?
What are IPCs?
Bulk material weighed out- Correct quantities
Initial mix and agitation of liquid- Time, speed, Shear, temperature, Water quality.
Dose into bottles through filling lines- Weight dispensed, fill volume, filling speed and pressure.
Application of bottle lids- Torque sensors, presence of lids
Labelling- Variable data, position and challenge tests.
Secondary packaging activity- Into carton, variable data, challenge tests, checkweigh (spoons/syringes/ PILs).
Tertiary packaging.
What are common compression defects? How are they caused?
Capping/Lamination- Air in tablet, overcompression. Moisture in granule.
Picking- Poor quality punches/ residue sticking on punches, moisture.
Breakage- Too fast take off, damaged tooling
Edge damage- Burrs on tooling.
Embedded material- Chem/Phys/Micro contamination. Charred granule.
What are common coating defects?
Peeling, mottling- Coating solution issue, temperature issue, gun position issue, atomisation pressure issue.
Loss of ID- Could be compression issue from tooling or over coating.
What are the typical excipients in a solution formulation?
Purified water
Solubility enhancer
Flavour
Colour
Preservative
PH buffer
What are the typical excipients in a suspension formulation?
What ‘state’ can suspensions be presented in?
What do syrups have as a defence against contamination?
Solvent- Syrup/ Water
Disperse solid phase
Viscosity enhancer
Taste enhancer
Colour
Suspending agent
Co-solvent
Preservative
De-flocculated- Hard to suspend
Flocculated- Easy to suspend
Syrups have low water activity (high sugar) therefore low aw.
What are typical excipients in emulsions?
Oil in water/ Water in oil
Viscosity enhancer
Density modifier
Emulsifying agent/ Surfactant
Preservative
What is the constituency of a cream? An ointment?
Cream = 50:50 water:oil
Ointment = 20:80 Water:Oil
What are quality risks associated with oral liquids? What is guidance for manufacture?
Microbiological- multi use and non sterile.
Annex 9- Liquids, creams and ointments
- Closed systems
- Cleaning is critical
-Max hold times
What is the USP dissolution acceptance criteria?
S1
6 units tested, Each unit is not less than Q + 5%
S2
6 Units tested, Average of 12 units Equal to or greater than Q
No unit less than Q -15%
S3
12 units tested, average of 24 units Equal to or less than Q
No more than 2 units Q -15%
No unit less than Q -25%
