The purpose of this article is to provide a brief guide for scaling up of coating process be it by perforated pan coating (Accela Cota) or by fluid bed (Glatt/Aeromatic) Process Technique.
The critical process parameters (CPPs) used/employed for a submitted ANDA batch Scaled Up from the Formulation product development may not be workable for a scaled-up commercial batch in larger equipment.
This article describes how to theoretically calculate the starting operating parameters when scaling up a process. The starting parameters will most likely need to be adjusted to achieve the desired results.
The Practical Tips section offers practical things to be considered when scaling up a process.
This May 2022 I paid a visit to Bangladesh on my arrival in Dhaka, Bangladesh I paid a visit to the Pharma Expo (19-21 may). There I met two gentlemen, Pharmaceutical Product Dev elopement Scientists working for a very reputed Pharmaceutical Company in Bangladesh.
With my expertized in Pharmaceutics as Product and Process Development Scientist in the US and a former FDA senior CMC reviewer, they wanted to have a professional discussion and advise on a specific process related issue which they were facing, during their scaling-up of a tablet product from its successful submitted ANDA to its commercial batch in large equipment for aesthetic coating of a generic tablet in Accela Cota type pan coating system.
Following are the general information and characteristics of the drug product for the scientific purpose discussion only without disclosing the actual names of the product, and its manufacturer.
1. Dosage Form: Film Coated Tablet
2. Purpose of film coating: Aesthetic
3. Coating System: Ready Mix Aqueous Powder, to be reconstituted by dispersing into water by stirring/mixing.
4. Coating Equipment: Accela Cota type perforated coating pan with spray gun system.
5. Delivery of coating suspension, either by using peristaltic pump or pressurized pot.
6. Substrate for coating: Uncoated Compressed Tablets (UCT)
7. Drug Load; Moderate
8. Specific API related Characteristics to be noted for the coating issue: Somewhat a little hydrophobic in nature.
9. Coating Issue: Due to the hydrophobic nature of the API and its moderate drug load in the drug product, i.e., the uncoated tablet, there was an issue of film “peeling off” in some of the coated tablets noted both during the product development as well as for the mid-scaled exhibit batches production stages.
The issue was resolved and/or brought to acceptance by employing sorting of the peel-off defective film coated tablets during packaging.
10. However, for the commercial batch tablets when they scaled into large equipment i.e. coating pan they were facing problems of higher number of defective tablets which was not possible to rectify or control just by employing sorting of defective tablets during packaging.
11. Listening to their problem we discussed the following points and suggestions towards the resolving and/or remedy for the issue:
A. Critical Parameters for Pan Coating Process:
- Air flow –CFM (cu.ft.V. /min)
- Air velocity - ft./min
- Air temperature - degrees F or C
- Total amount of liquid – kgs/Lts.
- Spray rate - g/min
- Atomizing pressure - psi
- Tablet Bed distance - inches/mm
- Number of Spraying Guns & distance from bed
B. Theoretical Scale Up
- Use same inlet temperature
- Use same velocity - velocity calculation Air flow ft2./min, Ft2 of gun distributor = ft./mi
- Calculate total amount of liquid per kg of product processed and maintain
- Calculate spray rate per CFM and maintain
- Maintain same liquid droplet size by adjusting air pressure as required
- Maintain nozzle distance above bed
- All above factors to achieve the same product temperature
C. Practical Tips:
- Visually achieve same cascading (turning of tablets in the pan)
- Note in small R&D machines (up to 20 liters) the spraying gun nozzle may be closer to the tablet bed. The lower liquid addition rate and smaller spraying gun nozzle will produce a smaller droplet size to compensate.
- The nozzle distance may need to be adjusted upwards when scaling up from small R&D to larger systems.
Drying Process:
A. Critical Parameters:
• Air flow ft. /min Air velocity - ft/min
• Air temperature degrees F or C
• Bed distance
• Product Characteristics
B. Theoretical Scale Up:
• Use same inlet temperature
• Use same velocity - velocity calculation
• Keep bed depth the same
C. Practical Tips
• Visually achieve same cascading of the tablet bed
• Keep the same bed distance if equipment design allows between the coating pans.
Summary / Achievements:
Both of the scientist called and informed me that they had a detailed discussion about the issue with the Film Coating System Manufacturer/Supplier and have had resolve the issue by their technical support team for the scale-up of the product.
Thus applying/following above scale-up factor for CPPs of the coating process in the larger equipment have achieved good results. Now the rejects are less than 10%. Actual results < 5% by employing sorting at packaging stage.
