In this Ardena Insight, we explore advanced crystallization techniques that transform racemic mixtures into enantiopure substances. These approaches ensure higher purity and targeted efficacy, playing a key role in the development of safer, more effective drugs.
With extensive expertise in drug substance development and solid state research, Ardena provides tailored solutions to support your chiral drug development needs.
Toxicology studies conducted under Good Laboratory Practice (GLP) are a crucial element of preclinical development, as the resulting safety profile drives the selection of the dosing range of subsequent first-in- human studies. While specific regulatory guidelines exist on the quality criteria of drug substance (DS) batches intended for clinical use, there are no such guidelines for preclinical DS. This Ardena Insight aims to provide a conceptual framework to achieve appropriate quality for DS batches used in GLP toxicology
studies.
Process safety is paramount in drug substance synthesis, especially when scaling up reactions involving hazardous conditions or reagents. At Ardena, we prioritize safety-by-design, using advanced techniques like reaction calorimetry and dose-controlled reagent addition to ensure safe, efficient, and scalable chemical processes.
In this Ardena Insight, we showcase how smart chemical design mitigates risks and enhances safety during synthesis. Learn how our expertise helps navigate the complexities of scaling up hazardous reactions.
Polymorphism in pharmaceuticals may affect drug product (DP) development, clinical studies, manufacturing, quality and stability. Therefore, it is mandatory to gain knowledge of the polymorphic behaviour of active pharmaceutical ingredients (APIs) in the early development phase by performing polymorph screen programs.
The Importance of Polymorphism
in Drug Development, crystalline APIs often exhibit the “polymorphism” phenomenon, meaning that different crystalline arrangements of an API are possible in the solid state. The API’s polymorphic behaviour can significantly affect its physical properties.
Polymorphic transformations can be prompted in DP manufacturing by physical processes, including compression, grinding, milling, processes involving solvents and moisture, or under storage conditions. Unexpected changes in polymorphic form may affect the quality and efficacy of the final DP and dramatically impact patients.
The most notorious example of polymorphic conversion affecting DP quality and efficacy is the Ritonavir case Form I, the only solid form of Ritonavir known in 1996, was marketed as a liquid formulation in hydroalcoholic mixtures. In 1998, precipitation from the DP solutions was noticed. This precipitation affected the API bioavailability as a lower amount of drug was present in the solution. Due to this inconsistency in the DP, Abbott had to remove the oral capsule formulation from the market. Investigations revealed that the emerged solid was a more stable polymorph, hence less soluble, known now as Form II. Eventually, the issue was solved, and the product returned to the market as a gel cap formulation. The discovery and reformulation of Ritonavir cost $250 million.
This whitepaper covers the issues related to polymorphism in drug development the benefits of experimental polymorph screen studies.
In this Ardena Insight, we explore how polymorphism impacts pharmaceutical development and patient safety. Different crystalline forms (polymorphs) of an API can change its properties, stability, and bioavailability. For example, Ritonavir faced market withdrawal when a new, less soluble polymorph reduced its effectiveness, requiring costly reformulation.
With extensive expertise in polymorph screening and solid state research, Ardena ensures the quality and success of your drug development programs.
Efficient supply of investigational medicinal products (IMPs) is key to ensuring patients are dosed on time and clinical trials run efficiently. In addition to the IMP, a wide variety of materials are needed to support a clinical trial, including placebo drug product, comparator drug product and ancillary supplies (e.g. diagnostic tests, medical equipment, consumables, etc.). In early-phase clinical trials, all these materials are typically shipped from different suppliers to the clinical centers. The hospital pharmacy staff then prepares prepare tailor-made patient kits that contain IMP, placebo and/or comparator drug product and the ancillary materials.
In this Ardena Insight, we highlight how the European Medicines Agency (EMA) empowers small and medium-sized enterprises (SMEs) through scientific advice and early regulatory dialogue. These initiatives help SMEs define their development strategy and streamline clinical timelines during drug development.
Since the creation of the EMA SME Office in 2005, pharmaceutical companies with fewer than 250 employees and annual turnover below €50 million have gained access to tailored regulatory, financial and administrative support. By 2017, over 1,800 companies had registered, demonstrating the growing impact of this dedicated platform.
At Ardena, we guide emerging biotechs through regulatory pathways, helping you make the most of EMA incentives and accelerate your innovation.
In this Ardena Insight, we explore the critical role of solid-state screening in identifying stable polymorphs during drug substance (DS) development. Polymorphs, crystalline forms with the same chemical structure but different molecular arrangements—can dramatically impact solubility, dissolution, flow properties and overall processability.
Inadequate understanding of DS solid-state behavior can lead to unintended polymorphic conversions during processing or storage, affecting manufacturability, bioavailability and clinical outcomes. Switching between polymorphs during clinical development may also trigger the need for costly bridging studies to satisfy regulatory requirements.
At Ardena, we help you strike the right balance, providing expert guidance on when and how to invest in solid-state screening. Our tailored approach ensures that you mitigate risk without incurring unnecessary cost, aligning your development strategy with both scientific and regulatory expectations.
In this Ardena Insight, we address the challenge of poor aqueous solubility in early-phase drug candidates and the formulation strategies designed to overcome it. As most compounds emerging from modern pipelines show limited solubility, enhancing absorption after oral administration becomes a critical goal.
While a variety of technologies exist to improve solubility and dissolution, no universal solution applies. Formulation choices must align with the drug’s physicochemical properties, permeability and dose. In early development, priority is given to approaches that support high drug loading, simple manufacturing, and flexible administration.
Ardena offers expert guidance to help you navigate formulation decisions for poorly soluble compounds, optimizing performance while accelerating development timelines.
In this Ardena Insight, we explore the strategic formulation of powder-filled capsules in early-phase drug product development. This widely adopted dosage form offers flexibility in dosing, ease of administration, and efficient blinding and taste masking, making it ideal for clinical studies.
By combining the active pharmaceutical ingredient (API) with selected excipients, Ardena creates optimized powder blends to enhance capsule manufacturability and performance. Our approach supports key quality attributes such as content uniformity, chemical stability, and disintegration, whether capsules are filled manually or at high speed.
With deep expertise in early-phase development, Ardena delivers reliable and scalable powder blend solutions tailored to your formulation needs.
In this Ardena Insight, we examine the growing role of oligonucleotides (ONTs) as therapeutic agents and the analytical strategies supporting their development. Since the approval of the first ONT drug in 1998, the field has rapidly advanced, with most market approvals occurring in the past four years.
ONTs combine features of both chemical and biological drugs, posing distinct development challenges, from selective tissue targeting to potential immunogenicity. While preclinical safety evaluation often follows small molecule guidelines, ONTs may trigger immune responses, requiring additional assessments. Their quantification in biological matrices also demands techniques commonly used for biologics.
At Ardena, we apply industry-standard methodologies to assess plasma concentration, tissue distribution and immunogenicity, ensuring robust support for your oligonucleotide development programs.
