News – We inform you regularly
RaDes is well prepared to serve its customers during the coronavirus pandemic

For two months now, life and work have been strongly influenced by the effects of the Corona pandemic.

At RaDes, we took early action and prepared ourselves. Anticipating and mitigating risks is a well-established practice for us. We are stocked with important materials (eluents, excipients) and hold our meetings virtually to avoid non-essential contacts.

An important finding is that it has paid off that we have invested in a powerful IT infrastructure from the very beginning: every employee has a notebook, data and analysis instruments can be securely accessed from home. Our laboratory operations continue in accordance with official regulations and a “backup team” working from home is in place to ensure business continuity and to be reliably available for our customers.

We take the situation seriously in order to protect the health of our employees and to act far-sighted and socially responsibly. We also do not lose sight of what was important before “Corona” and is crucial for the future: many things that make up good development work will continue to exist. Some things will change. The use of modern technology and digitalisation is changing from “nice to have” to a must have in many areas.

Finally, we would like to take this opportunity to thank our customers, suppliers and business partners. During this time, we have had many positive experiences of friendly and constructive cooperation and commitment to move things forward together in spite of obstacles.

Internship Project on Rheology

As of May, Manasse Feichtinger started a six-month internship at RaDes as part of his compulsory training as pharmacist. Manasse studied pharmaceutical sciences at the university of Marburg; in addition to that, he is a trained laboratory technician with experience in the analysis of semi-solid formulations.

At RaDes, Manasse is going to investigate rheological characteristics of semi-solid excipients and formulations, including oscillatory studies that allow deeper insights to the inner structure of materials, as well as thermo-rheology.

A particular focus is to what extent materials from different suppliers, which all comply with pharmacopeial specifications, show rheological differences that may be relevant for stability, process development, and performance. In addition, it will be investigated how rheological features of pure structure-giving excipients relate to their performance after incorporation in a formulation.

In RaDes’ second year of existence, this is our first student project. As we are committed to the development of talents, innovation, and the ambition to understand semi-solid formulations more and more systematically, we expect that more will follow!

RaDes has implemented Germany’s first Phoenix™ Robotic Diffusion Station with dry heat diffusion cells

Lack of control over variability factors can compromise data quality of in vitro release testing and cause ambiguity in the assessment of skin permeation.

We are proud of having implemented Germany’s first Phoenix™ RDS (Robotic Diffusion Station) with dry heat diffusion cells and being able to offer the benefits of this technology to our customers.

Its advantages versus the traditional technology of in vitro permeation testing include a significantly better temperature control provided by the Phoenix dry heat system as compared to circulating water baths systems. As diffusion is a function of temperature, this improves data quality. Similarly, a superior control of mixing speed is achieved. In addition, reduced maintenance and faster setup making it more economical.

Many thanks to Bruna Lousada from Teledyne Hansen Research and Severin Schweisthal & Antony Wozniak from Cole Parmer for the great collaboration and support!

www.hansonresearch.com/diffusion-testing/phoenix-dry-heat-systems

Petra Lohmann joins RaDes as Head of QA

We are very pleased that Dr. Petra Lohmann joined the RaDes team at the beginning of January 2020 as head of quality assurance.
Petra Lohmann has more than 20 years of experience in quality control and quality assurance in responsible positions, which makes her extensively familiar with quality requirements for pharmaceuticals, medical devices, cosmetics and biocides.
She is responsible for the development and maintenance of the quality management system at RaDes and offers consulting services and expert statements in the field of quality management.
Further information is available at: https://rades-development.com/en/about-rades/team/dr-petra-lohmann/

RaDes in 5 min, 42 sec

RaDes war eingeladen, sich auf der „Ins Netz gegangen“-Veranstaltung von Life Science Nord zu präsentieren. Die einzige Regel des Events, das am 27.11.19 in Lübeck stattfand, war: die Präsentation darf maximal 6 Minuten dauern. Michael Herbig, Geschäftsführer von RaDes, hat die Firma in 5 Minuten und 42 Sekunden vorgestellt und sich über die interessanten Diskussionen mit anderen Netzwerkmitgliedern im Anschluss gefreut!
Unter “RaDes bei Life Science Nord” finden Sie unsere Präsentation, für die Sie sich so viel Zeit nehmen können, wie Sie möchten.

Unser Chemielaborant für herausragende Leistungen ausgezeichnet!

Am 20.09.2019 wurde unser Mitarbeiter Janek Giebel von der Industrie- und Handelskammer zu Lübeck für seine herausragende Leistung in der Abschlussprüfung zum Chemielaboranten ausgezeichnet. Wir gratulieren ihm dafür recht herzlich und freuen uns, dass er unser Team mit seiner sehr guten Arbeit bereichert! Alles Gute!

RaDes presented poster on rheological characterization at Skin Forum in Reims

On 23 – 24 September Melanie Köllmer and Michael Herbig attended the Skin Forum in Reims, France. They enjoyed the scientific program with many interesting and relevant contributions and the inspiring discussions with other participants. Also, our poster “Differences in shear viscosities in the non-plateau region of the viscosity curve and implications for rheological method development and release testing of semisolid products” was well received and led to interesting discussions. For more information on services we offer around rheological characterization of formulation have look at our attached flyer.

Welcome aboard, Janek!

As of July, Janek Giebel has joined the RaDes team! He very successfully finished his apprenticeship to become a chemical laboratory technician in June 2019. During his training he already collected 3 years of experience in the analysis of semi-solid formulations.

Janek will mainly support us in analytical work (HPLC, UPLC, MS) as well as in galenic development and testing of liquid and semi-solid products.

We are happy that Janek is part of our team!

Expansion of our analytical equipment

After a successful first year we have extended our modern analytical equipment with an additional Waters ACQUITY™ UPLC™- H-Class with PDA & QDa (single mass spectrometer) detectors. The new system is also equipped with a solvent selection valve (6 mobile phases) and a column manager (up to 4 columns) and is therefore ideally suited for method development as well as for the analysis of large sample quantities.

All our HPLC and UPLC™ instruments are operated with the latest version of the chromatography data system Empower™ 3 (Service Release 3) from Waters GmbH to ensure high quality data management.

The new equipment allows us to further increase our capacity and flexibility in handling customer projects.

1 Year of RaDes!

At the beginning of July 2018, the history of RaDes began with the set-up of the laboratories and the creation of the website. In September the founding team was complete, in November the laboratories were fully operational. And after one year we are an established, growing development service provider!

We are grateful for the many positive experiences and collaborations and would like to thank our customers, partners, friends and look forward to further collaborations!

Three new publications by RaDes scientists

In the first months of this year, three research papers were published by RaDes scientists. These address different aspects with high practical relevance for the systematic development of liquid and semi-solid formulations:

The first paper published was a systematic evaluation of the Skin PAMPA model (‘Investigation of the Compatibility of the Skin PAMPA Model with Topical Formulation and Acceptor Media Additives Using Different Assay Setups’). In this, the general compatibility of the model with non-aqueous formulation systems was demonstrated and solvent concentrations above which there is a risk of extraction of lipids from the membrane were established. In addition, the potentials and limitations of a modified setup placing the donor on top were described.
DOI: https://doi.org/10.1208/s12249-019-1305-3

Furthermore, the influence of the aqueous concentration of betamethasone dipropionate on its stability in emulsion gels was investigated. It could be shown that with increasing emulsifier concentration more active substance was distributed into the water phase which causes increased degradation. The methods and insights pave the way to formulation options to stabilize hydrolysis-prone actives by “entrapping” them in the oil phase. DOI
DOI: https://doi.org/10.1016/j.ijpharm.2019.02.044

In order to determine the emulsifier content in the water phase, a new method for quantifying polysorbate 80 was developed. This means that polysorbate 80 can also be determined in concentrations far below the critical micelle formation concentration. Using a DoE approach, it was also possible to determine how the oleic acid contained in this highly complex mixture can be reliably determined in the presence of isomeric C18:1 acids.
DOI:  https://doi.org/10.1016/j.chroma.2019.04.015

If you have any questions or comments or if you see potential how our methods and insights can be helpful in your projects, please do not hesitate to contact us: info@rades-development.com or +49-40-57004180

POSTER AWARD AT ANNUAL MEETING OF THE SOCIETY FOR DERMOPHARMACY

Julia Puschmann of RaDes GmbH was awarded the first prize of the “Hans Christan Korting-Nachwuchspreis für Dermopharmazie” at the annual conference of the Society for Dermopharmacy and had the opportunity to present her work in two short talks. We congratulate Julia on her award!

She received it for her poster entitled “How does the emulsifier concentration affect API stability in emulsion gels and skin penetration?”. It demonstrates that it is possible to stabilize hydrolysis-prone actives in aqueous creams if the active is lipophilic and you use the right formulation technology! Using the active betamethasone dipropionate, she elucidated the underlying mechanisms, such as the influence of emulsifier concentration and the correlation of degradation with increasing free drug concentration in the aqueous phase.

In addition, she demonstrated that the skin penetration, tested on the pig ear with the Hamburg model (https://doi.org/10.1016/j.ejpb.2015.03.030), was further influenced by a changed saturation of the formulation upon addition of co-solvents.

Meanwhile, her corresponding paper was also published: (https://doi.org/10.1016/j.ijpharm.2019.02.044).

If you have any questions or comments, don’t hesitate to contact us: info@rades-development.com

RaDes presents at „APV Expert Workshop: Emulsions“

Emulsions are important systems in drug delivery, especially for topical application, but also orally and parenterally. The APV workshop on 01 to 02 April 2019 will provide a comprehensive insight, including formulation, characterization and processes.

Michael Herbig of RaDes will give a presentation on: ”Cream 2.0“ – Enhancing scope, performance and robustness of emulsions through rational design”. He is presenting new insights in distribution phenomena in emulsions and their effects on stability and performance, on effects of emulsifiers, consistency adjusting systems and approaches to modify skin penetration.

Find the program details here: https://www.apv-mainz.de/fileadmin/dateiablage/apv-mainz/Seminare/oeffentllich/6767_Emulsions_experts.pdf

If you’re interested in further information, don’t hesitate to contact us: info@rades-development.com.

Rheometer for formulation characterization implemented

With the implementation of the rheometer MCR 102 by Anton Paar GmbH we have added a new tool for formulation characterization to our equipment list. With this instrument we can perform both oscillatory and rotational measurements of semisolids and liquids. By variation of the chosen system (plate/plate, cone/plate, cylinder/beaker) we can obtain information on structure and behavior under stress of different formulation types.

Oscillation rheology allows prognosis for long-term stability and behavior under stress e.g. pumping into the storage vessel. Additionally, the influence of stress on the formulation can be measured. Using special methods, also the recovery of the structure after stress application can be shown. Does the formulation reach its structure before the stress  application or is the formulation changed due to the destruction of the inner structure? Furthermore, the impact of varying concentrations, batches and suppliers of excipients can be compared to collect data on critical quality attributes e.g. the behavior under thermal stress.

Various formulations regarding type (emulsions, creams, ointments etc.), excipients (critical quality attributes) and storage conditions can be compared to evaluate the best possible prototype for your development and to support the trouble shooting of existing products.

If you have any questions, don’t hesitate to contact us: info@rades-development.com

Waters Acquity™ UPLC™ H-Class PLUS implemented

Since end of October, a Waters ACQUITY™ UPLC™ H-Class PLUS with PDA eλ (UV/VIS) & QDa (single mass spectrometer) detectors expands the analytical equipment at RaDes GmbH.

We can cover a broad range of customer needs – from method development using Quality by Design, the transfer of analytical methods between HPLC and UPLC™ technology, up to the fast and reliable analysis of a large sample size.

What do these detectors stand for?

PDA eλ: highly sensitive photodiode array UV/VIS detector with an extended wavelength range between 190 nm to 800 nm to receive spectral information up to the visible range (e.g. to investigate discolorations) and for a robust quantification of compounds over a wide linear range.

QDa: Mass spectrometer (size of a UV/VIS detector) for peak tracking, quantification of compounds at a low concentration level or with a low UV absorption, assessment of co-elution.

The system contains next a solvent selection valve (six additional solvents) a column manager (four columns) to significantly save time and resources during method development.

All our HPLC and UPLC™ instruments are connected to the latest version of Empower™ 3 (Service Release 3) of Waters GmbH to ensure high-quality data management.

Particular benefits for our customers include:

1) Analysis of poor UV-absorbing molecules such as macrolides and peptides – a trend in dermatology.
2) Analysis of low dose formulations – another trend in dermatology.
3) Faster and better method development for classical HPLC:

  • The method is developed using a DoE approach with a UPLC™. If necessary, co-eluting peaks are separated by mass spectrometry using the QDa detector and can therefore be precisely evaluated.
  • The optimum conditions are selected from the design space considering resolution, run time and robustness.
  • in silico transformation into a HPLC method using DoE.
  • experimental confirmation on classical HPLC.
New insights into the optimization of preservation of emulsions

The preservation of creams and emulsions is often challenging. On the one hand, dermal drugs must be preserved in accordance with pharmacopoeia regulations in order to actively reduce microorganisms introduced. On the other hand, the number and concentration of the preservatives used should be kept as low as possible in order to optimize the compatibility of the formulation. Generally, depending on the product category and region (EU / USA), there are also maximum concentrations for the use of preservatives. Furthermore, a number of potential incompatibilities of preservatives with other formulation ingredients or primary packaging should be considered.

In the recently published study “Correlation of antimicrobial effects of phenoxyethanol with its free concentration in the water phase of o / w-emulsion gels.” (Puschmann et al., Eur J Pharm Biopharm (131) 152-161, 2018, www.sciencedirect.com) scientists from RaDes GmbH in collaboration with the Pharmaceutical Technology of the TU Braunschweig were able to gain new insights with high practical relevance for the optimization of preservation systems in emulsions.

We were able to establish a new method to accurately determine the concentration of the widely used phenoxyethanol preservative in the oil and water phases. In addition, it was possible to distinguish between free and micellar bound preservative within the water phase. As we expected, antimicrobial efficacy does not depend on the total concentration of the preservative but on the free concentration in the water phase. This in turn can be significantly influenced by the composition of the oil phase, by co-solvents in the water phase and by emulsifier type and concentration.

Our methods and insights make it possible to develop preservative systems faster and more robustly and to optimize the overall system in terms of antimicrobial performance, technical robustness and skin tolerance. Last but not least, based on this, the number of germ load tests necessary in the development phase can be purposefully reduced, thereby saving time and costs. This approach can also contribute significantly to the development of new, optimized preservatives.