An Alternative Method Of Drug-Excipient Characterization

The development of pharmaceutical products requires thorough testing to ensure the compatibility of active pharmaceutical ingredients (API) and excipients. Isothermal microcalorimetry (IMC) offers a faster, less labor-intensive alternative to traditional methods like HPLC for assessing these interactions during early and late-stage formulation development. IMC monitors heat flow at a constant temperature, detecting chemical or physical incompatibilities by comparing the thermal activity of individual components with that of their mixtures.

Unlike HPLC, which can take weeks to produce results due to labor-intensive processes like elevated temperature studies and periodic sampling, IMC screens samples in 24–48 hours. IMC experiments reveal potential incompatibilities through shifts in heat output curves, as seen in the Maillard reaction between APIs containing amines and lactose, highlighting chemical incompatibility. Conversely, compatible alternatives like mannitol show no significant interaction in IMC data, streamlining excipient selection.

IMC also applies to liquid formulations, where it can quickly assess excipient effects on API stability under accelerated conditions. Beyond initial development, IMC aids in identifying alternative excipients to address post-formulation issues or changes in excipient suppliers, ensuring continued compatibility and stability.

By rapidly eliminating incompatible excipients and reducing reliance on more labor-intensive methods, IMC accelerates the formulation process, enhances efficiency, and reduces costs. Its ability to screen both physical and chemical interactions makes it an indispensable tool in modern pharmaceutical development, ensuring high-quality formulations with minimal resource expenditure.