Solitek offers development stage-appropriate advice to help you reduce the risk of failure during the later development stages and to maximise the returns from potential out-licensing opportunities.
Solid state characterisation
Solid state characterization is key to understanding the physical properties of solid materials. These physical properties can have an impact on the material’s bulk properties, formulation performance, processability, stability and appearance.
A deep understanding of the physical properties of the molecules will be useful to understand the potential challenges that that form may encounter during development or manufacturing and will feed back into the design of the active ingredients to optimize the physicochemical attributes that will make them more likely to succeed depending on their specific application.
Understanding the crystallinity behavior of the molecule, as well as its thermal properties, hygroscopicity, etc. will help us evaluate the fitness of the current form for development and will establish the basis against which different batches of material produced should be measured.
Solid form screening and selection
Solid form screening and selection is critical for the successful development of active ingredients. New chemical entities are facing increasing challenges in their physical properties (solubility, dissolution rate, ability to crystallize, stability, etc), and the selection of the right crystalline form is a fantastic way to optimize their physical attributes. Plus, it offers and excellent entry to novel intellectual property.
Salt or cocrystal selection, where physicochemical properties of the molecules can be modulated to suit your development strategy. The formation of a salt or cocrystal will depend on the ability of the drug candidate to ionize (pKa) or in the ability to exploit other interactions (H-bonds or stack interactions) respectively. Other factors depending on the specific application will be taken into consideration to design a screen with high chances of success.
In the pharmaceutical industry, regulatory authorities require that companies have full control on the physical properties of their development candidates, to ensure that no changes will occur during later development, manufacturing or even commercialization that may affect the performance or safety of the drugs. Performing a polymorph screen early during development will help you greatly to manage the risks associated to solid-solid transitions or new potential polymorphs appearing later that may alter the behavior of the drug causing potentially large costs of re-working existing batches and potential losses of revenue if the drug has to be withdrawn from the market. A phase appropriate polymorph screen design will help you manage the risk without committing more resources that are necessary depending on the development stage of the drug.
Other less regulated industries can also benefit from the selection of an optimal solid form depending on the intended application.
A deep understanding of the physical properties of the molecules will be useful to understand the potential challenges that that form may encounter during development or manufacturing and will feed back into the design of the active ingredients to optimize the physicochemical attributes that will make them more likely to succeed depending on their specific application.
Understanding the crystallinity behavior of the molecule, as well as its thermal properties, hygroscopicity, etc. will help us evaluate the fitness of the current form for development and will establish the basis against which different batches of material produced should be measured.
Crystallization process development
Once a suitable solid form has been selected, the next step is to know how to reproducibly make this form using a robust and scalable process. As well as the polymorphic form, particle size distribution (PSD) and crystal habit are often key product attributes that affect performance or processability. Unfortunately, the PSD and crystal habit are often highly susceptible to changes as the process is developed and scaled.
Solitek can provide the key knowledge of solubility and crystallization kinetics, growth and nucleation, and how these are affected by chemical engineering factors, thereby avoiding surprises on transfer from lab to kilo-lab, pilot plant and manufacturing.
Early enabling formulation development
Through the synergy between solid state chemistry and formulation, we can add value to your pre-clinical project, while decreasing timelines. During preformulation, the physicochemical properties of the drug substance are investigated. Understanding the relevant physiochemical and biopharmaceutical properties determines the appropriate formulation and delivery method for pre-clinical and Phase 1 studies. Performed using small-scale analysis techniques, we can determine key characteristics of drug molecules even when solubility is low and drug material is limited.
Our experience and technical knowledge can rapidly identify molecule challenges with protocols which emphasize efficient use of resources. Applying our understanding of drug physicochemical properties, we can offer tailored and rational preclinical formulation development.
Using the Developability Classification System (DCS) as our framework, we examine how the physicochemical characteristic of a compound may affect oral absorption and bioavailability, determining risk and suggesting formulation strategies. Using a rapid excipient screening approach, we can provide preclinical formulations which enhance drug solubility and overcome in vivo sources of pharmacokinetic variability. In vitro testing using biorelevant models can demonstrate formulation abilities to promote supersaturation and resist unfavorable situations such as pH-mediated precipitation and food effects.
Training and consultancy
Our team of experts would be delighted to share their knowledge and experience with you. These services could be both theoretical and practical, and located either in Solitek’s site in Barcelona or at the customer’s choice of venue. Please contact us for more information.
