Tablets Flashcards
Talk us through a typical tablet formulation and manufacture? What are the CQAs and Critical/Key Parameters in this process?
Dispensing - Tolerance on weighing
Wet or dry granulation - wet or dry - Agitator speed, mesh size, liquid addition rate, CQA - Uniformity of content
Fluid bed dryer / Microwave drying - Drying temperature, mesh size and drying time, CQA - moisture
Blending - Rotation speed and time, CQA - Moisture
Compression - Fill volume, dwell time, compression force, ejection force and tooling, CQA - Tablet hardness and thickness, weight variation, friability, disintegration and appearance
Coating - Spray rate and pattern, drum speed, inlet air temperature and airflow across the tablet bed, CQA - Appearance (AQL 1250)
List the components of a tablet and give examples of each
Diluent - act as a fillers to increase weight and improve content uniformity. Common diluents starch and lactose
Glider - act by filling in the gaps on the surface to improve flow. Examples are colloidal silicon dioxide, magnesium stearate, and silica
Lubricant - reduce the friction between the tablet and the die metal surface to improve ejection from the die. Common lubricant is magnesium stearate
Binder - to facilitate bonding of powder particles during granulation. Examples are gelatine, water and starch
Disintegrant - aids mechanical break up of a compressed tablet into small granules upon ingestion
What would be the impact of over lubrication? What is typically used as a lubricant?
Magnesium stearate is a common lubricant. Over lubrication can lead to over coating of the granules with a lipid layer which will protect the tablet from breaking up as required within the body, which in turn will have an impact on bioavailability
Why are broken tablets a problem?
Impact to dissolution / bioavailability and delivery system e.g. if enteric coated - broken tablet would be more susceptible to disintegration in the stomach which may not be the target area
A company want to change the IPC limits for the moisture content of a granulate; what are the implications for the QP?
Is the IPC registered if so this will require a variation
What are the issues around controlling the end point in high shear and low shear granulators.
Granulation endpoint can be defined as the time when the granules reach the desired properties such as granule size distribution, flowability or bulk density, as stipulated by the formulator.
High shear, or very forceful, mixing processes uses high-speed impellers, and low shear mixing processes use flow, turbulence, and rotational force to combined miscible goods.
A high shear mixer has the following disadvantages:
It may cause degradation of powder, especially for fragile or thermolabile powders.
Over wetting may cause the production of large lumps.
Produces less compressible granules.
A narrow range of operation conditions.
The main disadvantages low shear granulation are the open nature of the equipment, the manual transfer of the materials being processed and the long drying times.
How could you control the endpoint in a fluidised bed drier?
The conclusion should be made based on drying temperature, air velocity and drying time. A IPC moisture sample can be taken at endpoint to confirm dryness.
What are the issues in a fluidised bed drier?
While fluid bed dryers are generally more gentle on the product, in some cases the material may experience some attrition and dust generation during fluidization, which could require additional measures in dust and air quality control. It may also make the fluid bed an unsuitable choice in some settings.
Disadvantages of Fluid Bed Dryer. A Possibility of Product Loss. Chances of Electrostatic Build Up May be High. Drying Sticky Material is Quite Difficult.
Poor drying performance: If the fluid bed dryers (FBD) is not drying the material properly, it may be due to insufficient air flow or an incorrect temperature profile. Check that the air flow rate is within the recommended range and that the temperature profile is appropriate for the material being dried.
What factors affect the bioavailability of active from solid dosage form?
Correct composition, homogenous mix, blending time, Coating, broken tablets
Describe the manufacture of a wet granulated tablet.
Dispensing, binder make up and addition, granulation, screening, drying, lubricant addition and blending, compression, coating, bulk packing
What is “capping” and what causes it?
The term tablet capping is used when either the upper or lower part of the tablet separates horizontally either partially away from the main body or completely to form a cap when ejected from the press or during the handling process.
Excessive turret speeds, rapid decompression, and elevated pressure force can cause it.
Name a source of information on tablet ingredients
Patient information leaflet
What is the greatest risk of (bacterial) contamination in a tablet?
Water content, raw materials e.g. maize starch, binder solutions, hold times
In terms of a dry compaction process for making tablets – what tests would you typically do as in process controls?
Hardness, thickness, weight, friability, disintegration
What grade of water would you use in wet granulation?
Purified water
