Polymorph Screening
Many pharmaceutical compounds are capable of forming more than one crystalline phases, which are known as polymorphism. Different polymorphs have different physicochemical properties, and polymorphs may even affect physical properties and lead to lower bioavailability. Therefore, it is critical to evaluate the polymorph of a compound and select the optimal solid form for the following production. BOC Sciences is committed to helping our customers clearly understand the polycrystalline form of a product, select a specific crystal form of an API, and reduce the chance of risk at later stages of development.
Benefits of polymorph screening
- Reduce the risk of failure during development
- Meet regulatory requirements
- Enhance intellectual property
Why is polymorph screening important?
1) Polymorphs have different physicochemical properties that may affect their biological activity, pharmacokinetic properties and stability
2) Your product may not be thermodynamically stable in its current polycrystalline form
3) Lots of polymorphic forms are protected by intellectual property rights. Identifying polymorphs in the API can protect the relevant intellectual property associated with a new API
4) Generic drug companies try to identify available polymorphs that are not subject to patents so that they can launch a non-infringing generic product
Figure 1. Decision tree of Polymorph screening. (Dey, R.; Chowdhury, D. R. 2020)
Our Services
To make it easier and better for researchers, BOC Sciences provides polymorph screening service in a competitive fashion. We have provided a more efficient way to increase the number of new drugs, greatly shorten the R&D cycle, and reduce the development costs
- We support multiple crystallization methods, including solvent evaporation, cooling, agitating slurry, vapor diffusion, rapid precipitation, melt quenching, and amorphous transformation, to perform the polymorph screening experiments
- For a standard screening program, our team performs more than 200 experiments with more than 20 solvents. The identified crystal forms are then characterized after scale-up production, and their relative thermodynamic stability will be determined by competitive slurry experiments
- To improve the completeness of polymorph screening and reduce the risk of missing stable forms, we are capable of applying our CSP technique to locate low-energy structures as explicit targets for screening experiments
- We also compare the experimental results with the energy rankings generated by the calculations to confirm the relative stability between crystal forms.
Polymorph screening process
The purpose of polymorph screening is to try to find all possible crystal forms by small-scale crystallization and to select a stable form that can be manufactured and formulated into dosage forms. Our teams have developed a reliable polymorph screening workflow:
1) Discovery of all possible polymorphs
2) Assessment of the stability of these forms
3) Study of the physical and chemical properties of the main candidates and select one for further development
Figure 2. Examples of physical properties that may differ among different forms. (Dey, R.; Chowdhury, D. R. 2020)
Polymorphism characterization methods
At BOC Sciences, a number of techniques are available for identifying solid forms of a compound:
- XRPD for preliminary study of polycrystalline morphology
- Dissolution/solubility testing
- TGA and DSC to understand thermal behavior
- Microscopy to assess crystal habit
- Hot-stage microscopy to correlate with events observed in TGA and DSC
- GVS to assess hygroscopicity
- UPLC and 1H NMR to assess chemical purity, structural integrity and residual solvent levels
- Storage under ICH guidelines to assess stability
- Thermodynamic solubility and kinetic dissolution rates in any relevant media
- Single-crystal X-ray diffraction
Amorphous screening
Crystalline polymorphs do not allow for sufficient water solubility and amorphous forms may be required. BOC Sciences has in-depth experience in the numerous techniques applied to induce the amorphous forms of APIs
Figure 3. Rational for choice/selection of the methods for the preparation of polymorphs. (Dey, R.; Chowdhury, D. R. 2020)
Why choose BOC Sciences?
Our dedicated CMC team has provided tailored solutions to our clients from engagement to launch. With many years of industry experience, we provide clients with the following:
- Comprehensive, integrated CMC services with a flexible service model that grows with your programs
- Knowledgeable industry experts who deliver scalable, actionable insights
- World-class facilities and equipment that remain at the forefront of the global pharmaceutical research, analytical and development standards
- Our comprehensive services support products at every stage of the product lifecycle, from early-stage discovery to full commercial cGMP manufacture
- A focus on risk management that is designed to ensure completion of your technical goals
BOC Sciences provides professional, rapid and high-quality services of polymorph screening at competitive prices for global customers. Personalized and customized services of polymorph screening can satisfy any innovative scientific study demands. Our clients have direct access to our staff and prompt feedback to their inquiries. If you are interested in our services, please contact us immediately!
Reference
- Dey, R.; Chowdhury, D. R. Review of Pharmaceutical Solid Polymorphism: Preparation. Characterization and Influence on Performance of Drugs. 2020. 2(1): 33-48.
