TABLETING 67
REFERENCES 1
www.fda.gov/downloads/drugs/
guidances/ucm070305.pdf. 2
www.gea.com/de/products/ lighthouseprobe.jsp.
In many cases, the inlet gas is not humidity controlled, which means its drying ability will depend on the external environmental conditions (summer/ winter effect). A third source of variability is tablet production, which is often done in campaigns. Batch number one may be done in completely clean equipment, resulting in a yield of approximately 95% (a lot of material sticks to the surfaces), whereas the following batches may have yields of 100%. FDA was well aware of these types of issues when it launched the PAT initiative. With the objective of modernising pharmaceutical production, manufacturers and agencies were asked to focus on critical quality attributes (CQAs). In fluid bed drying, this is clearly the final moisture content, as well as (albeit to a lesser degree) parameters such as gas flow rate, inlet gas temperature and drying time, which were key elements of the classical validation approach.
Fluid bed
product shelf-life. However, the next unit operation in the process train is tableting, which in the majority of cases demands a granule-to-humidity ratio at the upper end of the range to minimise problems such as capping. So where does the variability come
from in a validated process such as this? It shouldn’t happen. Te simple answer
is that all potential sources of variability are rarely covered by the validation. Raw materials are often stored in non-classified areas such as warehouses. For instance, when starch – which has a high moisture equilibrium – is added to a process, the actual amount of solid material may vary according to the humidity at which it was stored: a variable percentage will be water.
Importance of measuring critical parameters If the critical parameter can be measured directly, the other parameters can play a smaller role. With end-of-drying product moisture content, this means that we need a method to determine the value directly. As proven many times in the food or chemical sectors, this can be done using NIR spectroscopy. Plus, as we only want to monitor one value, there’s no need for complex chemometrics. A simple calibration over the relevant moisture values is enough. With the Lighthouse Probe, GEA offers a proven, off-the-shelf solution to avoid window fouling.2
When
combined with a basic NIR device, moisture levels can be determined in real- time, drying can be terminated when the desired moisture level has been reached and offline testing can be relegated to ancient history. Welcome to the 21st century.
Dr Harald Stahl is with GEA.
www.gea.com
www.scientistlive.com
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75 |
Page 76 |
Page 77 |
Page 78 |
Page 79 |
Page 80 |
Page 81 |
Page 82 |
Page 83 |
Page 84
