Nanoscale Technique Measures Surface Physical Properties of APIs

Nottingham, UK (June 26)-Molecular Profiles created a poster that demonstrates the efficacy of its “nanoPASS” (nanoscale predictive analytical screening solution) technique to characterize an active pharmaceutical ingredient’s (API) surface energy. The study used carbamazepine as a model compound to investigate the surface energy of three polymorphs. The samples were investigated before and immediately after size reduction by micronization, and after micronization and storage at ambient laboratory conditions for one month.

Researchers prepared carbamazepine forms I, II, and III and confirmed their identity using powder X-ray diffraction and Raman and infrared spectroscopy. Surface free-energy measurements were based on the adhesive interaction between an atomic-force microscope probe and single particles of carbamazepine. In each experiment, relative humidity was maintained at ~1%, and electrostatic charging was minimized. Measurements were made in a grid pattern across the surfaces of multiple particles. Researchers micronized the carbamazepine samples for 10 min with a Sturtevant (Hanover, MA) qualification micronizer using a grind pressure of 100 psi.

Results showed that the nanoPASS technique was able to discriminate between three polymorphs or carbamazepine at the single-particulate level and with nanoscale lateral resolution. Researchers also identified an increase in the surface energy following micronization. Surface energy reverts to its previous level after storage in ambient conditions.

The nanoPASS technique allows data to be acquired from a few milligrams of material, and researchers can apply it at an early stage of drug development.

Surface free energy is an important consideration in drug formulation because it is a major factor in adhesion and cohesion. For example, this behavior must be understood when developing inhalation formulations because the size-reduction process can change an API’s surface energy significantly.

Molecular Profiles provides contract research services to the pharmaceutical, biopharmaceutical, and biomedical industries. The company presented the poster, titled “Measuring Surface Physical Properties of Pharmaceutical Materials for Inhalation: Physical Changes During the Size Reduction Process,” at Respiratory Drug Delivery 2008 in Scottsdale, AZ. Molecular Profiles introduced the nanoPASS service platform to its nanoscale analytical services offering earlier this year.