How to predict what happens to long-acting injectables?

First author Ge Fiona Gao explored subcutaneously administered injectables as part of her PhD project

We are very happy to announce that Ge Fiona Gao just got her second first-author paper accepted by the Journal of Controlled Release. Our investigation of the drug release from PLGA microspheres highlights the need for biorelevant conditions to simulate degradation effects and predict bioavailability. Our international team of authors from Germany, Singapore, and Japan established in vitro-in vivo correlations for two drug formulations of tacrolimus. The formulations were tested in biorelevant medium in presence of protein background using the DR technology. To establish the IVIVC, a drug recovery model and a membrane permeation model were used and the fraction released in the in-vitro system was calculated. Mechanistic understanding of the physiological processes was gained by means of an in-silico model reflecting the absorption mechanisms in the subcutaneous tissue. The interplay between release, drug diffusion, lymphatic transport, and degradation plays a key role in the performance of injectables that remain in the subcutaneous tissue for a longer time period. Once production is over, the manuscript will become available under:


Gao GF, Ashtikar M, Kojima R, Yoshida T, Kaihara M, Tajiri T, Shanehsazzadeh S, Modh H, Wacker MG (2020); Predicting drug release and degradation kinetics of long-acting microsphere formulations of tacrolimus for subcutaneous injection, J Control Release (Accepted for publication) 


#releasetesting #morethandissolution #NUS #FacultyOfScience #wackerlab


Beilstein Talk: Nanomedicine

Established by the Max Planck Society in 1951, the Beilstein Institute is a non-profit organization promoting the chemical sciences. Today it publishes the free-of-charge Beilstein Journal of Nanotechnology. During the COVID pandemic, researchers made their results accessible in times of crisis and we all found value in science without barriers. This is why I am happy to support the foundation by giving the first in a series of Beilstein Talks. On the 18th of November 2020, 9 pm Singapore time (2 pm CET) I will present:

“Nanomedicine at the crossroads: Why good chemistry is not enough”

Please join the virtual event and hear my critical reflection on nanotechnology research and why interdisciplinary approaches are needed to improve current design strategies…

CLICK HERE TO REGISTER

#sciencewithoutbarriers #releasetesting #wackerlab #nanomedicine

#SavingThePlanet?

Everyone wants to have access to medicines! For many years, we know that an aging population together with the quality of life we got used to leads to higher consumption of pharmaceuticals. But there’s also a rising concern that pharmaceutical drugs pollute our planet. Environmental scientists do not hesitate to say how disappointed they are with the pharmaceutical industry. Many comments indicate a total lack of understanding of the way our healthcare system works. Once a medicine has passed the clinical trials and market approval has been granted by a national authority, a company has no freedom at all to “just change the recipe”. Along this line, nanotechnology has been described to have a strong negative impact on different ecosystems.
So how are we saving our planet? Our latest research paper written by Fabian Jung was just accepted by Environmental Research. It uses release testing, a method commonly applied by the pharmaceutical industry in development, to select drug formulations that are likely to succeed during clinical trials. We are combining this technique with computer-based simulations (ISERA model) and a lifecycle assessment to pre-select the excipients used in production. Because we are stopping the use of non-sustainable excipients very early in drug development, we still have all the freedom we need to make medicines more sustainable. Additionally, we present the application of nanomaterials to reduce environmental pollution. To do so, we combine smart technologies to identify drug formulations that are effective and safe in patients without posing a risk to the environment.

Read the full story here


#ScienceSavesThePlant #EnjoyReading #WackerResearchLab #ExplainMyResearch

Illustration of drug product development using ISERA and LCA.

Advances in Interdisciplinary Pharmaceutical Research

The AAPS student chapter of the National University of Singapore organizes a symposium together with Monash University putting interdisciplinary research in the spotlight. The event takes place on the 23rd of September. What would be more inspiring than bright young minds presenting their vision of the future? Please watch out for the latest announcements of NUS Pharmacy.

#AAPS-NUS #NUSPharmacy #NUSFacultyOfScience

Simulate SubQ

Our latest research article on drug release testing of a long-acting depot formulation was just accepted by the International Journal of Pharmaceutics. This is great work by the young first author Ge Fiona Gao. One year ago she won a Best Abstract Award of the AAPS Annual Meeting, now she has done a tremendous job showing the influences of the physiological environment on formulations that remain at the injection site for several weeks.
The release assay elucidated the influence of proteins on microparticle release and how they affect discrimination between different batches of drug products. Even without affecting solubility, proteins stabilize particles and may affect the performance in the subcutaneous tissue. A mechanistic model helped us to understand the influences of such parameters and formulation characteristics on pharmacokinetics. Why does it matter? Without understanding what are the major drivers of drug release there will always be a high risk of failure when testing new long-acting therapeutics for chronic diseases.

#SaferMedicines #EnjoyReading #ExplainMyResearch

The PBNB model: Unlock your PK data

Today, our manuscript on the Physiologically-based Nanocarrier Biopharmaceutics (PBNB) Model was finally accepted for publication by the European Journal of Pharmaceutics and Biopharmaceutics. I explained the purpose of this model in my talk during the Explain-My-Research Virtual Conference in May 2020 and will go more into detail during a Live Webinar organized by Malvern Panalytical in July. Rather than providing a ‘convenient fit’ only, the model is designed to link the pharmacokinetics of nanocarriers to a physiologically-based distribution. Interesting parameters you may obtain with this model are, for example, the targeting capability and the mean residence time of the nanocarrier in the blood plasma. A lowered plasma concentration often indicates that more drug has been released from the carrier and is not available for targeting any more. The PBNB model recognizes such changes and calculates how much carrier-bounded drug is accumulated before this release happens. Expressed as a fraction of the total dose, this is the targeting capability (Ftarget) . The mean residence time of the carrier (MRTc) in the blood plasma indicates how much time the delivery system had for this accumulation process and is a marker for targeting accuracy.

Some of the simulations our PBNB model is capable of are provided on the servers of our collaborator isee systems.

Guest judge @ SPDS

I was very happy to act as a guest judge for the Society for Pharmaceutical Dissolution Science. For the last 10 years, my group has been passionate about developing novel release assays and it was good to have a conference putting this important part of drug product development in the spotlight. Students from all over India submitted their work on drug release testing. Congratulations to the finalists.

Save the Environment

It is really difficult to publish translational manuscripts these days, but this is a prime example of a good collaboration between pharmaceutical and environmental sciences. As pharmaceutical scientists, we sometimes have to use a certain material to facilitate drug therapy. But if we have a choice and more than one coating or one polymer actually works, why not choose the one which is best for the environment? This study helps you sort that out.

Predicting Nanomedicines

A wide variety of models have been established to predict the performance of nanomedicines for the peroral route of administration, but only a handful for injectables. Liposomal temoporfin has been evaluated in a phase I clinical trial. This investigation was focused on the prediction of the performance of liposomes in humans using preclinical in vitro and in vivo data. Congratulations to our young researcher Laura Jablonka who is responsible for this great accomplishment. Also, it is a prime example for international collaborations by involving researchers from Germany and Singapore…