Hi All,
I kindly need your help to provide input on below 2 cases
Case 1:
I am currently working on formula transfer of suspension with key excipient/suspending agent of Veegum HV. The current developed process differ in sequence and parameter compared with sending site/legacy process. In early trials and registration batch we found no issue on suspension’s stability. However in verification batch prior validation we found flocculation/bulk separation issue which after investigation attributed to abrupt pH adjustment using 28% sol of citric acid (in past batches we always follow gradual add and mixing until pH target achieved). We rectify it by adding specific procedure/OPL for operator, then next 3 batches succeed.
Question:
Is citric acid known excipient which has incompatibility with Veegum HV? We realize that this legacy formula has bulk pH <6 while Veegum HV normally used in pH>6.
CASE 2:
On 4th batch we face similar flocculation issue albeit less severity compared to case 1. The only obvious step different was on the charging process of execipients. Process was:
- Veegum hydration
- Add sorbitol & glycerin
- Add main excipients in succession: Citric acid (initial add, the pH adjustment would be at the end of process) > sodium benzoate > Simethicone > Lecithin > Tween 80
- Add API
- Add Kollidon 25
The difference in recent failed batch was on step 3 that the add of all 5 excipient was SLOWLY
QUESTION:
Which excipient works as stabilizer? May I say that because of slow add the stabilizer failed to work and the citric acid create flocculation first?
In long term I might need to change the sequence.
Thank you in advance