Molecular Profiles present paper on measuring APIs
A poster detailing techniques for measuring the surface physical properties of pharmaceutical materials for inhalation has been presented by Nottingham-based contract service organisation Molecular Profiles.
A poster detailing techniques for measuring the surface physical properties of pharmaceutical materials for inhalation has been presented by Nottingham-based contract service organisation Molecular Profiles.
The poster demonstrates the ability of nanoPASS (nanoscale Predictive Analytical Screening Solution) to characterise the surface energy of an API material. nanoPASS, an innovative new service platform, was launched earlier this year as a new addition to Molecular Profiles" nanoscale analytical services offering. This poster entitled "Measuring Surface Physical Properties of Pharmaceutical Materials for Inhalation: Physical Changes During the Size Reduction Process" was recently presented at Respiratory Drug Delivery 2008, Arizona, USA.
The interactions of active pharmaceutical ingredients with excipient particles in an inhalation formulation determine the efficiency of the device. For example, unwanted agglomeration of particles or adhesion to device components can have a negative impact on dose uniformity. Such interactions must be carefully optimised to ensure adequate separation of the API and excipient particles upon activation. The surface free energy is an important consideration when formulating a pharmaceutical material since this is a dominant component of adhesion and cohesion phenomena. This can be particularly important when considering APIs used in inhalation formulations since the size reduction process can cause significant changes in surface energy.
The aim of this study was to investigate the surface energy of three polymorphs using carbamazepine as a model compound. Samples were investigated before and immediately after size reduction by micronisation, and after micronisation and storage at ambient laboratory conditions for one month. This work highlights the application of nanoPASS as a comprehensive suite of complementary analytical techniques designed to optimise solid state selection of APIs and proved further insight into the formulation of APIs and excipients.
In the application detailed in the poster, Carbamazepine Forms I, II and III were prepared and confirmed by Powder X-ray Diffraction (PXRD), Raman and Infrared spectroscopy. Surface free energy measurements were based on the adhesive interaction between an atomic force microscope (AFM) probe and single particles of carbamazepine. Humidity was kept to a minimum (~1% RH) and electrostatic charging was minimised prior to each experiment. Measurements were made in a grid pattern across the surfaces of multiple particles. Micronisation was performed using a Sturtevant qualification microniser with a grind pressure of 100 PSI for 10 minutes.
The poster demonstrates the ability to discriminate between three polymorphs or carbamazepine at the single particulate level and with nanoscale lateral resolution. In addition, the researchers identified an increase in the surface energy following micronisation, a change, which begins to reverse after storage in ambient conditions. An understanding of such behaviour during this type of processing is crucial in minimising undesirable formulation attributes. Data can be acquired from a few milligrams of material, hence can be applied at an earlier stage of development. This information can aid the rapid screening of pre-formulation materials to understand how the physical properties of an API may change during processing.
