Pharmaceutical polymorphism analysis: a service to identify the forms

The pharmaceutical polymorphism is a critical issue for development, technology transfer, quality control, and supplier change management. A variation in crystalline form can alter solubility, stability, bioavailability, process behavior, or even batch compliance. In this context, drug analysis is not limited to simple chemical identification: it must make it possible to distinguish an anhydrous form from a hydrate, a crystalline form from an amorphous state, or to compare multiple batches, raw materials, or intermediate products. The laboratory supports pharmaceutical manufacturers in investigating a batch-to-batch difference, qualifying a new supplier, studying a non-conformity, or documenting material equivalence. Depending on the project objective, the study may focus on identifying a form, comparing analytical profiles, or providing data useful for a Pharmaceutical Product Deformulation approach.

A pharmaceutical polymorphism issue can arise in many situations: dissolution deviation, stability drift, change in appearance, variation in compressibility, filtration difficulty, abnormal drying behavior, batch-to-batch differences, or qualification of a second source. It may also be investigated after a process change, variation in crystallization conditions, a solvent change, or the appearance of an unexpected deposit. In the pharmaceutical industry, these weak signals can have a direct impact on product performance and on regulatory control of the dossier.

Identifying a form relies on complementary physicochemical techniques. DSC makes it possible to observe thermal transitions, melting, and certain recrystallization events. TGA provides information on mass loss, which is especially useful for suspecting the presence of water or residual solvent associated with the solid structure. FTIR or infrared microscopy can be used to compare chemical signatures and certain differences in molecular organization. Depending on the issue, other approaches may be used to study purity, associated compounds, traces, or inorganic species. The goal is not to use a single technique in isolation, but to build a coherent demonstration.

The laboratory applies expertise in material characterization tailored to the challenges of the pharmaceutical industry. The added value lies not only in producing instrumental results, but in cross-interpreting them to answer a specific industrial question: same form or not, potential impact of a change, need to go further, or whether the data are sufficient to make a decision. This approach helps speed up decision-making while reducing the risk of misinterpretation.

The analytical approach relies on combining complementary techniques to obtain a robust understanding of the solid state. The goal is to determine whether two samples present the same physicochemical signature, to highlight a phase transition, to identify the presence of a solvate or hydrate, and to link these observations to the product’s properties. This approach can be used in R&D, quality investigations, during scale-up, a site change, or in the context of a contradictory expert assessment. In addition to solid structure studies, the laboratory can also investigate impurities, contaminants, or trace elements through services such as ICP Pharmaceutical Analysis or the study of Unknown Particles in Pharmaceutical Products.

The laboratory designs a test plan tailored to the client’s level of expectation: simple comparison of two samples, identification of an unknown form, study of compliant and non-compliant batches, or more in-depth characterization of a pharmaceutical solid. Interpretation is decision-oriented: confirm equivalence, objectify a difference, prioritize hypotheses, and provide results that can be used by quality, CMC, analytical development, or purchasing teams. This support approach is part of a technical assistance and Filab RD Service framework.

Comparing two forms or several batches relies on cross-checking the results: thermal profiles, spectral signatures, volatile content, crystallinity behavior, and, if necessary, targeted complementary analysis. This approach makes it possible to distinguish a real structural difference from a simple variation in secondary composition. It is particularly useful for raw materials, intermediates, excipients with complex behavior, or active ingredients sensitive to moisture, solvents, or process conditions.

The results are presented in a clear and actionable way for batch comparison needs, supplier qualification, nonconformity investigations, or development support. The laboratory can also combine the solid-state study with other investigations into composition, impurities, contamination, or deformulation, depending on the need. This ability to make the material speak is part of a broader approach highlighted through Filab Faire Parler La Matiere Au Service De La Rse.

Send your samples, specify your issue, compare two batches, qualify a new supplier, investigate a non-conformity, confirm a pharmaceutical polymorphism hypothesis, request a testing strategy, interpret cross-checked results, and secure a development or quality control decision.