It’s not rpm, it’s your dissolution specs – Q value + time point.
Sceptical?
Well here’s a case study that makes this obvious.
In this study, dissolution was run on Progesterone 100 mg Soft gelatin capsules. Dissolution profiles of two Test batches with different API particle sizes – Test 1 and Test 2 – were compared against that of the reference product.
They were tested using the same dissolution method conditions.
What did the profiles show?
The batch that was bioequivalent to the reference product – Test 1 – produced a dissolution profile overlapping the reference.
Test 2, the bio inequivalent batch, separated early and stayed significantly different up to 30 minutes.
By 45 minutes, all the three batches showed near complete release
So if you adopt a ‘generally accepted’ IR specification of 75(Q) at 45 minutes – you’ve basically chosen a timepoint where all the batches look comparable- Even Test 2 that wasn’t bioequivalent!
On the other hand, a spec like 80(Q) in 30 minutes would reject the bio inequivalent Test 2 batch- because that’s where separation still exists- making it discriminatory by definition.
Takeaway:
We focus a lot on discriminatory method conditions (apparatus, agitation rate, medium). And rightly so.
But in routine QC, what actually decides whether a batch passes or fails is the specs.
Dissolution specs= Q value + timepoint can either:
Expose meaningful differences in acceptable and unacceptable batches
or
Mask them
Discriminatory power isn’t only built into method parameters (apparatus, agitation rate, medium). It is ALSO built into the dissolution specification – because that’s what turns dissolution results into a pass/ fail decision on product performance.
So, if your dissolution specs came from a template or ‘this is what we always do’ place…pause.
And ask yourself: 𝘞𝘰𝘶𝘭𝘥 𝘵𝘩𝘪𝘴 𝘥𝘪𝘴𝘴𝘰𝘭𝘶𝘵𝘪𝘰𝘯 𝘴𝘱𝘦𝘤𝘴 𝘥𝘪𝘴𝘤𝘳𝘪𝘮𝘪𝘯𝘢𝘵𝘦 𝘣𝘦𝘵𝘸𝘦𝘦𝘯 𝘣𝘢𝘵𝘤𝘩𝘦𝘴 𝘮𝘢𝘯𝘶𝘧𝘢𝘤𝘵𝘶𝘳𝘦𝘥 𝘸𝘪𝘵𝘩 𝘮𝘦𝘢𝘯𝘪𝘯𝘨𝘧𝘶𝘭 𝘥𝘪𝘧𝘧𝘦𝘳𝘦𝘯𝘤𝘦𝘴 𝘪𝘯 𝘤𝘳𝘪𝘵𝘪𝘤𝘢𝘭 𝘱𝘳𝘰𝘤𝘦𝘴𝘴 𝘱𝘢𝘳𝘢𝘮𝘦𝘵𝘦𝘳𝘴 𝘢𝘯𝘥 /𝘰𝘳 𝘤𝘳𝘪𝘵𝘪𝘤𝘢𝘭 𝘮𝘢𝘵𝘦𝘳𝘪𝘢𝘭 𝘢𝘵𝘵𝘳𝘪𝘣𝘶𝘵𝘦𝘴?
Read also: R&D Guide to Dissolution Specification Setting
Resource Person: Pearl Pereira Nambiar