The Power of In Silico Polymer Screening for Drug Formulation

Picture polymers in drug formulation as the coating of a chocolate praline. They create a matrix for the active pharmaceutical ingredient (API), similar to how a praline’s outer shell encases its delicious center. This polymer « coating » does more than just bind the ingredients; it precisely regulates the release of the API, much like the controlled flavor release in pralines for highest taste experience.

The Importance of Polymers in Drug Formulations

Polymers play a crucial role in drug formulations, particularly in ensuring physical stability and tailoring drug release behavior. Once a drug molecule reveals poor water solubility or release behavior, polymers become essential in improving these characteristics. By combining the right polymer with the drug, formulators can modify the drug’s behaviors and enhance its effectiveness.

For instance, if a pill is not as effective as desired due to poor absorption, adding a polymer will help improving bioavailability. Polymers can facilitate fast or sustained drug release, target specific regions of the gastrointestinal tract, and fine-tune the desired release profile. With a wide range of synthetic and natural polymers available, formulators can tailor drug formulations to meet specific requirements. While polymers offer these significant advantages, the traditional methods of selecting them present several challenges.

Limitations of Traditional Formulation Development

In the initial stages of formulation development, formulators often grapple with the question: Which polymer or combination of polymers will yield the desired release profile and stability for the drug? Historically, the pharmaceutical industry has relied on high throughput screening to address this question. This approach involves testing numerous polymer and active pharmaceutical ingredient (API) combinations to identify optimal formulations based on release kinetics, stability, and resistance to environmental factors such as humidity.

However, this trial-and-error methodology has inherent limitations. It is time-intensive, resource-draining, and lacks a systematic approach from the outset. Formulators frequently find themselves navigating in the dark, relying on experimentation to stumble upon the optimal formulation.

Transforming Formulation Through Data-Driven Methods

To overcome the shortcomings of traditional methods, the pharmaceutical industry is nowadays transitioning towards a quality by design framework. In silico polymer screening is at the forefront of this paradigm shift, enabling formulators to design formulations with desired properties even before entering time cost-expensive lab experiments.

By utilizing few preliminary experimental data, amofor’s in silico polymer screening provides a more accurate and efficient model for polymer selection. It considers factors such as net intermolecular interactions of the API itself of the drug molecule. This means it measures how strong are repulsive forces, known as Thunderbolts interactions, of an API molecule. Essentially, it assesses how strongly the API molecule repels other molecules. Additionally, it considers the hydrogen bonding capacity, charge, and polarity of each molecule. Tailored specifically for each unique molecule, this method effectively identifies the most suitable polymers for creating amorphous solid dispersions (ASDs).

One of the key advantages of our in silico polymer screening is that this approach eliminates the need for sharing the chemical structure of the API with us, thus also overcoming legal and compliance concerns. Instead, it leverages experimental data such as solubility profiles to determine physicochemical interactions. Another advantage of our in silico polymer screening is the reduction in the number of key experiments required. Unlike traditional methods that involve countless combinations, amofor’s in silico screening only requires five solubilities in different organic solvents and a differential scanning calorimetry measurement for understanding crystal properties. This streamlined process saves time, resources, and API materials, while delivering validated rank order for polymer and drug load selection.

In recent partnerships with leading pharmaceutical companies we applied the in-silico polymer screening approach to the latest drugs in development. In these projects, we predicted the intermolecular interaction profiles and identifiedindividually the strongest polymer for ASD development. This was subsequently experimentally confirmed by our clients, demonstrating the effectiveness of our approach.

Validation through Marketed ASD Formulations

To assess the validity of in-silico screenings for ASD polymer selection, we at amofor conducted a comprehensive study investigating marketed ASD formulations, including Ritonavir (Norvir) and Sporanox (Itraconazole). The goal was to determine if the polymer identified through in-silico screening corresponded to the polymer used in the marketed formulations.

Remarkably, the results revealed a strong correlation between the polymer identified through in-silico screening and the polymer employed in the marketed ASD formulations. Notably, Ritonavir (PVPVA64) and Sporanox (HPMC) formulations contained both one of the best interacting polymer, as predicted by our independent in-silico screening process.

Advancing Drug Development with Pioneering Physics-Based In-Silico Modelling

While other companies perform solvent-based film casting screenings for polymer selection, in silico polymer screening sets itself apart as a unique data-driven approach. This technique is rooted in factual, experimentally validated data, delivering a level of precision and reliability in drug formulation that is unparalleled and currently exclusive to our technology.

If you’re a drug formulator striving for innovative solutions to overcome formulation challenges, we invite you to explore the possibilities of in silico polymer screening. Bring a handful of experimental data and propel your drug development endeavors to new heights.

Dive deeper into the topic? Check out this excellent overview book chapter Structured Development Approach for Amorphous Systems or the publication Thermodynamic Phase Behavior of API/Polymer Solid Dispersions if you want to learn more about the potential this  effective approach.

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