Meet the Expert: Pearl Pereira- Nambiar
To continue our Meet the Expert series, we're delighted to feature Pearl Pereira Nambiar, a seasoned pharmaceutical development expert with over two decades of specialized experience in analytical development strategy and regulatory science. Pearl has built exceptional expertise across diverse dosage forms – from oral and injectable to ophthalmic and topical formulations – with a particular focus on bridging the critical gap between analytical data and regulatory expectations.
Q: Could you please introduce yourself and tell us about your background?
A: I have over two decades of experience in pharmaceutical development, with a focus on analytical development strategy, drafting development reports, and responding to regulatory deficiencies.
I’ve worked across a wide range of dosage forms – oral, injectable, ophthalmic, and topical – bridging the gap between analytical data and regulatory expectations. A large part of my role involves responding to complex deficiencies. I see these not as challenges to fix, but as opportunities to strengthen the science, improve risk anticipation, and build more robust development strategies going forward.
I’m also passionate about simplifying regulatory science. Through my LinkedIn content and masterclasses, I aim to make topics like dissolution testing, analytical development, and compliance strategy more accessible and actionable to professionals across the industry.
Q: In your experience with dissolution testing, which regulatory agencies tend to request specific formulations, and what trends are you seeing, particularly with softgel formulations?
A: Globally, there is a growing emphasis on ensuring that dissolution methods AND limits can reject potentially non – non-bioequivalent batches.
Soft gel capsules are deceptively simple. However, these formulations typically involve poorly soluble drugs suspended in oily or lipid–based matrices, which interact differently with the dissolution medium. Moreover, the drug release mechanism is far more complex compared to conventional hard gelatin capsules.
So, you can’t just plug in a standard dissolution method for ‘capsules’ and expect it to be meaningful. For softgels the risk of drug precipitation or shell-fill interactions is very real, especially under stressed conditions.
We often see situations where the drug performs well in vivo and meets bio-equivalence criteria, but the dissolution test fails during stability. That’s a red flag – not necessarily about product performance, but about dissolution method limitations. This underscores the need to identify critical method parameters that truly shift the needle with the in vivo drug release, rather than simply forcing discriminatory power where it doesn’t exist.
There’s also a clear push toward physiologically relevant pH. But this comes with challenges, especially when the soft gel collapses into an insoluble mass during dissolution testing, which means you must look beyond your trusty Type I or Type II apparatus!
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Q: What would you say are the main challenges you face in your role, especially when it comes to analytical method development for dissolution testing?
A: With complex dosage forms and increasingly sophisticated drug release mechanisms, dissolution method development is just as challenging as formulation design. But what often tops that challenge is having to present and justify the method effectively in the regulatory dossier.
There’s a common misconception that only the development needs to be solid. But without clear, technically sound writing, even good science can get lost in translation. Your documentation must connect the dots between the drug’s behavior, the rationale behind every parameter, and its relevance to the in vivo drug release, so that the numbers tell a coherent development story.
Another challenge is the lack of ‘standard’/ detailed guidance for certain novel/ complex dosage forms. In such cases, you are not just developing a method – you are also defining the standard.
Q: Could you share a specific success story where you overcame a particularly challenging technical or regulatory hurdle? What made it challenging, and how did you approach the solution?
A: One particularly challenging yet rewarding case involved an injectable nanosuspension. At first, it seemed like a standard task – develop a dissolution method and set appropriate specifications. But once we started working on it, the challenge turned out to be something else entirely: demonstrating that dissolution was NOT the right quality control test for this product.
The formulation was designed to rapidly distribute in the body after intravenous administration, where drug release was influenced by multiple biological processes, not simply by solubility in an aqueous medium. Extensive experimental trials, including dialysis-based methods, showed that none reliably reflected the product’s in vivo performance without introducing variability or artificial constraints.
After a detailed evaluation, we showed that attributes like particle size and surface characteristics were more predictive of in vivo performance than in vitro dissolution.
The irony was that the regulatory expectation is typically to prove method is discriminatory. Here, we had to prove, using data and clear technical writing, that the dissolution method wasn’t the right discriminator. That required decoding the drug’s release mechanism in vivo, aligning with the in vitro behavior, and framing our argument within a risk-based development strategy.
The approach was well received by the regulatory agency, and the method was not mandated for routine quality control. This outcome reinforced something I strongly believe in that sometimes, success in analytical development means knowing when to or NOT to test and having the science to stand by it.
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Q: Can you walk us through one of the trickiest analytical problems you’ve encountered? How did you troubleshoot and resolve it?
A: One that really stands out involved dose-proportional tablet formulations, where we had applied for a strength–based biowaiver. Being dose-proportional immediate release formulations, we expected dissolution profiles to align. But when we ran the data, the F2 values were well below 50, which was unexpected.
We tried pooled dissolution to rule out if this was due to strength-wise solubility differences – we compared a single high-strength tablet against multiple lower-strength tablets (sum = high strength) – the profiles still didn’t match.
While reviewing the dataset, I noticed that the tablet shapes varied across strengths. That got me thinking – could it be geometry influencing surface area and, in turn, dissolution? I calculated the surface-area by volume (SA/V) ratio for the two strengths and applied this as a correction factor to the results, and voilà, the adjusted dissolution profile curves aligned remarkably well with f2 values above 50.
Interestingly, the idea to explore the SA/V ratio as a possible solution came from a dissolution conference I had attended, where Dr. Muhaned Al Hindawi spoke about its impact on dissolution profiles. That insight stayed with me and turned out to be the key to solving this challenge.
Disclaimer: The views expressed here are Pearl’s own and do not represent those of her current or past organizations, or any regulatory authority. They are based on her personal experience and interpretation within the scope of her professional work.
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