Episode 8 Arkopharma (Water in Pharmaceuticals)

Episode 8 Arkopharma (Water in Pharmaceuticals)

Today I'm joined by Fabienne Latournel-Perrot, a French research and development team manager at Arkopharma Laboratories. In this special episode, we're stepping out of Water in Food to learn about water in pharmaceuticals and nutraceuticals and how moisture sorption isotherms are applied to these industries. Let's hear what Fabienne has to say on Water In Food ...

Transcript

Zachary Cartwright (00:00):
I'm Zachary Cartwright. This is Water in Food.

Fabienne (00:02):
Active ingredients are known to be sensitive to temperature and humidity. Predictive stability is very useful to anticipate the loss of active ingredients in the formulation over time. A conventional stability study takes between three, five years. So a big benefit for our company on time and on money. Practice makes perfect.

Zachary Cartwright (00:26):
Today I'm joined by Fabienne [Letournel-Perreau 00:00:28], a French research and development team manager at Arkopharma Laboratories. In this special episode, we are stepping out of Water in Food to learn about water in pharmaceuticals and nutraceuticals and how moisture switching isotherms are being applied to these industries. Let's see what insights Fabienne has for us. Hi, Fabienne. Thanks for being on the show today.

Fabienne (00:51):
Thank you for having me on.

Zachary Cartwright (00:53):
Of course. Why don't you tell us a little bit about yourself, and what you do and where you're from?

Fabienne (00:59):
Yes. I grew up in the Southwest of France and I've always been interested in science and technology. I graduated in oceanography and I got the opportunity to work in a marine research center in Brittany, so it's located in Northwest of France.

Fabienne (01:21):
I worked as a laboratory technician in the environmental department over three years. I carried out the chemical analysis of the seawater samples picked up along the French coast during oceanographic campaigns. The purpose was to assess the effect of human activities on the marine environment. It was really a great experience. At the end of my employment contract, I decided to study food science at university. This [inaudible 00:01:57] me as an exciting and innovative field, offering many opportunities to work in a R&D laboratory.

Fabienne (02:11):
Later I got the opportunity to work at Arkopharma. I got hired at Arkopharma in the chemical analysis laboratory in 1991, so far time. And Arkopharma... I'm not so young. Arkopharma is a pharmaceutical laboratory located in Southeast of France, pretty nice area. Arkopharma was founded in 1980 and has been the first company to manufacture and to release plant-based supplements in capsules with a pre-dose from the phytotherapy market study to take off. Today our company is the market leader in Europe.

Fabienne (03:09):
In 1991, I started to take part in the development of dietary supplements. That was a brand new project and it was very, very exciting. We brought out a wide variety of products, cereal bars, syrups, tablets, capsules containing plant-based ingredients, vitamins, minerals, fatty acids. I developed analytical methods for the quality assurance service, which is in charge of ensuring that finished products meet the required standards. And besides, I ran studies on food supplements. It's an exciting job.

Zachary Cartwright (04:03):
Yep. Thanks for telling us about your background. It sounds like you've done a lot. How did you first get interested in food science? Why did you decide to go to school for food science?

Fabienne (04:17):
Because at this time, this industry was promising a lot of opportunities in research and development and financial resources too. I thought that it could be a very exciting job for an analyst.

Zachary Cartwright (04:49):
And has it been exciting for you?

Fabienne (04:51):
Yes. Yes. I'm a bit proud of my choice and I'm proud of my company.

Zachary Cartwright (05:04):
Good. I'm proud of my choice too. I think there's a lot of opportunities as a food science and it opens a lot of different doors that you don't really expect. As you started to work at Arkopharma and work in R&D, when did water activity become a part of your formulation process?

Fabienne (05:27):
Yes. The water activity has been taken into account for a long time, but mostly as a marker of the microbiological quality. But before we started to use the Vapor Sorption Analyzer, we didn't know much about the relationship between water activity and the chemical-physical stability in our products. We used to focus on moisture content that we considered as a factor of degradation in the products but it wasn't. But sometimes the degradation has not been observed despite an increased moisture content. So the concept of moisture content related to water activity has been clear. Once we started to use the VSA, the Vapor Sorption Analyzer, then we realized that water activity and moisture content have to be taken into account together. And this understanding improved our formulation process and the predictive stability. It was very, very important to understand that.

Zachary Cartwright (06:54):
So before you were using moisture sorption isotherms, you were running classic stability studies. What did that look like and how long did that take you?

Fabienne (07:07):
About [inaudible 00:07:10] stability studies. Yes. The purpose of the stability testing is to provide evidence on how the quality of a substance or drug product varies with time and the influence of temperature and humidity, oxygen, light. But in our case, temperature and humidity are the most degrading factors. A conventional stability study takes between three and five years. It's a bit lengthy. The finished product is stored in normalized climatic conditions in the laboratory, long-term, intermediate and accelerated conditions, and at regular time points, the required tests are carried out to ensure that the physical and chemical acceptance criteria are met. There's a difference between medication and food supplements. But because we have to prove, to give the evidence of the quality, stability of food supplements, we must run the conventional stability study.

Zachary Cartwright (08:39):
So you're using moisture sorption isotherms in addition to still doing some classic stability studies, is that correct?

Fabienne (08:48):
Yes.

Zachary Cartwright (08:50):
The benefit of the isotherm, if I'm not mistaken, is that, although these classic studies can take a long time, three to five years, you can get a lot of insight very quickly by using the moisture sorption isotherms for things like stability or shelf life and packaging. I also know that you are very interested in predicting the loss of active ingredients. Why is that interesting to your company and what benefits does this have for Arkopharma to know about your active ingredients?

Fabienne (09:27):
So as I said, as a conventional stability study on medication is definitely required by the authorities. For food supplements, the protocol is less conventional but we must give the evidence of this stability. That's why we carry out the classic stability study to predict the degradation. I have to say that we have been collecting a huge number of analysis data from stability studies conducted for more than 20 years. Sometimes this knowledge helps us to forecast the stability of a new formulation. Sometimes it doesn't. So the predictive stability is very useful to anticipate the loss of active ingredient in the formulation over time. This predictive stability is part of the formulation process. So the test results of the predictive stability can lead to change the formulation so you save time and money, of course. And therefore we are more confident about the stability of the finished product, of the shelf life, and the required long-term storage. The study is likely to meet the acceptance criteria. So it's a big benefit for our company on time and money and to feel more confident about the stability of the formulation of the product.

Zachary Cartwright (11:21):
And how would you say your predictions with moisture sorption isotherms, how do those predictions compare to your actual measurements? Do you see a lot of correlation there?

Fabienne (11:33):
Yeah. The prediction must be compared with the classic stability study. We start very recently, the APS, this predictive stability study. We have run accelerated predictive stability testing on active ingredients that we studied before in capsules so we have already a lot of data. These active ingredients are known to be sensitive to temperature and humidity. For some of them containing a mixed powder and capsules, the prediction is a bit overestimated to reach six months at 40 degrees Celsius and 75% average. That could be explained by the fact that at 40 degrees Celsius the relative humidity is over the critical water activity we measured in the capsule beforehand. But the prediction is completely right after storage of 12 months at 30 degrees Celsius and 75% on average and that's helpful. Again, we are going on improving the accuracy of the APS testing method for our products and practice makes perfect.

Zachary Cartwright (13:21):
Yes, that is definitely true. You mentioned critical points for your products. What are those critical points? Are those just water activities where you lose your active ingredient or are these also points where you have caking and clumping and some type of texture change? What are those critical points for your company?

Fabienne (13:46):
The most critical points for our products are the caking and the change of color or odor. But the most difficult challenge to overcome is the hygroscopicity of the products because we use natural raw materials, sometimes plant extracts. For example, plant extracts that contain a lot of carbohydrates are problematic because there are too much hygroscopic. To overcome this problem, you can add excipients, natural excipients, that can make the water activity lower in the mixture. So we try several formulations and put the prototypes in climate chambers so we can select the best formulation. But we also use the software, moisture resistor kit, and the mixing ingredient to get the total final isotherm of the different formulation. It saves time and we can select the perfect formulation.

Zachary Cartwright (15:54):
So you're using the DLP ingredient mixing tool, which essentially allows you to combine a bunch of different isotherms for different ingredients or different products, and then view your final isotherm and your predicted water activity, is that correct? And that's helping you to speed up your R&D process?

Fabienne (16:16):
Yes. Yes. But of course, we have to record all the isotherms of each ingredient. So we are building a type of library, we're working on it. It's very, very interesting too.

Zachary Cartwright (16:47):
Yeah. Building your own isotherm library is definitely a never-ending process, but it's very helpful when you have those isotherms for the things that you work with. What type of isotherms are you creating? Are you making DVS, dynamic vapor sorption, isotherms or are you creating DDI, dynamic dewpoint isotherms, or maybe a combination of both?

Fabienne (17:19):
We run both DDI and DVS isotherms because we work in close collaboration with formulation scientists. We start first with DDI isotherm, which is very useful for the formulation scientist because the critical water activity is the first essential information that the formulation scientist needs at the first step of the development. The DVS isotherm, in a way, it's more useful for the chemical analyst, I guess, because the DVS isotherm helps me to calculate and to predict accurately the water intake during storage in a particular climate condition over time. It helps me to set the shelf life, manufacturing, and storage conditions. It's very, very important. And also too, I can select the best packaging for the product.

Zachary Cartwright (19:07):
Okay, great. So it sounds like the DDI is what you're using to get that critical point and then DVS really comes into play for things like chemical stability or kinetics and also looking at shelf life. So having both of them at your fingertips seems like it's been really useful for you and your team, is that correct?

Fabienne (19:28):
Yes, of course. We have been working well with isotherm for one year, in fact. Constantly for one year.

Zachary Cartwright (19:41):
And still going. So from here, let's move away from isotherms and from being so technical, I just want to hear what are your goals for the rest of this year? Do you have any things that you're trying to finish up in 2020 at your company that you're excited about?

Fabienne (20:03):
For the next month?

Zachary Cartwright (20:06):
Can you believe we're almost done.

Fabienne (20:09):
No. Just there's so much to do for the next month. The food supplements market is very, very competitive, and requires to be innovative. We are working on a lot of new projects and new raw materials and it's very important for my team to upgrade its skill in predictive stability. We also want to get where we're working harder on this topic.

Zachary Cartwright (20:57):
If somebody wants to learn more about Arkopharma, where can they go? What's the best way to learn about your company?

Fabienne (21:11):
First Arkopharma manufactures and releases almost 300 health products in Europe and worldwide. You can visit our website arkopharma.com and discover our natural solutions in healthcare of our products, vitamins, minerals, royal jelly, and beauty, of course.

Zachary Cartwright (21:38):
Okay, great. Well, thank you for your time today, Fabienne. We really appreciate it. One last question. The holiday season is coming up this year and do you have any plans for the holiday season? With everything going on, is there something special that you usually do with your family that you won't be doing this year?

Fabienne (21:58):
We are looking forward to the 15th of December and we'll know if we go on with the lockdown or no so I don't have any plans for holidays.

Zachary Cartwright (22:20):
Yeah, me neither.

Fabienne (22:23):
I hope it will be okay, but I'm not very sure about this.

Zachary Cartwright (22:27):
Well, we're all in the same boat, Fabienne. I'm right there with you.

Fabienne (22:31):
Yes. Yes.

Zachary Cartwright (22:33):
Well, thank you again. We really appreciate this. I've really enjoyed learning about how you-

Fabienne (22:38):
Thank you [crosstalk 00:22:38].

Zachary Cartwright (22:39):
Yes, you're welcome. We will see you again.

Fabienne (22:42):
I enjoyed it.

Zachary Cartwright (22:42):
You're welcome.

Fabienne (22:42):
Thank you.

Zachary Cartwright (22:44):
I'm Zachary Cartwright. This is Water in Food. Find this podcast on Apple iTunes, Spotify, or wherever you listen to podcasts.




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