Powder Rheometry for Optimising Formulations for Tablet Compressiontresen.vscht.cz/kot/wp-content/uploads/2017/01/Powder-Rheometry-for... · In high shear wet granulation, the addition
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Due to their simple and convenient use, compressed tablets are the mostwidely used solid dosage form, representing 70% of all dispended medicines.
As well as providing the correct API dosage at the correct rate, the finaltablet must be easy to handle, administer and store. It should also be asuitable size, hardness, texture, stability and palatability.
In addition to the Active Pharmaceutical Ingredient (API), tablets contain anumber of inert materials/ excipients required to aid formulation. Theseinclude:
The Traditional Approach to Pharmaceutical Tablet Manufacture
Requires each batch process step to be validated and fixed, with qualityretrospectively tested.
Requires all potential variables (including raw material properties) to beconsistent, batch to batch, if quality is to be assured.
Most raw material specifications may list particle size distribution, density,water content and some chemical properties, but not particle shape, surfacetexture, surface energy, elasticity, or many other likely importantparameters.
These variables all influence bulk powder properties like flow, adhesion,compressibility – therefore perhaps it is not surprising that batch to batchproblems are often related to variation in raw materials.
Resistance of the tablet against an applied force until it breaks.
Tablets must be able to withstand the rigors of handling and transportationexperienced in the manufacturing plant, in the drug distribution system, andin the field at the hands of the end users (patients/consumers).
Manufacturing processes such as coating, packaging, and printing caninvolve considerable stresses, which the tablets must be able to withstand.
The mechanical strength of tablets is therefore of considerable importanceand is routinely measured.
Tablet strength serves both as a criterion by which to guide productdevelopment and as a quality control specification:
Too high – tablet(s) may not disintegrate within the specified time ormeet the dissolution specification.
Too soft – tablet(s) may not withstand subsequent handling such ascoating, packaging and shipping.
In high shear wet granulation, the addition of water and work (shear) resultsin larger, denser, more adhesive granules.
This means that more water and more work input results in higher flow energyas granules are harder to move (denser, larger, stickier and less compressible).
Two types of formulation considered in this study:
APAP – 90% API
DCP – 90% API
Process Variables
Water content varied to provide granules with different properties, fromunder-granulated to over-granulated (determined visually).
Screw speed varied to investigate it’s influence on granule properties.Settings chosen: 450, 600 and 750rpm.
Feed rate of dry powder feeder also varied for a limited number ofsamples. Settings reduced from 25kg/hr (standard, equivalent toConsiGma 25), to 20 and 15kg/hr.
Data showing the strong relationship between granule properties and a critical quality attribute of the tablet (hardness) for each type of granule (wet, dry, milled, lubricated)
2. The multiple process steps involved in tablet production, subject rawmaterials and intermediates to a range of different variables.
3. Each process operation provides the opportunity to adjust settings in orderto improve process efficiency and / or to alter the properties of the materialleaving that stage of the process.
4. With sufficient understanding of the relevant material properties and criticalprocess parameters, it is possible to employ a QbD approach to tabletmanufacture, ensuring the Critical Quality Attributes (CQA) of the tablets aremet.
5. Full characterisation of powder flowability and other bulk and particleproperties ensures the necessary information for QbD is available.
6. The FT4 Powder Rheometer from Freeman Technology has proven to be auniquely valuable instrument in these applications and has been widelyadopted across most powder processing industries worldwide.