Unprecedented Sensitivity for API

Crystalline Quantification using SONICC®

SONICC (Second Order Nonlinear Imaging of Chiral Crystals) is a novel imaging technique that offers unprecedented sensitivity in quantifying small molecule crystallinity. SONICC can be used to detect concentrations of crystalline APIs down to 0.03% in amorphous solid dispersions. Analysis is fast (< 1 second), no sample preparation is required, and can be performed on final form with excipients present.

 

Amorphous solid dispersions

 

The bioavailability of the active pharmaceutical ingredient (API) in a drug is typically a strong function of the solubility of the API molecule itself. When polymorphic forms of this molecule are present, the most stable one is usually crystalline. Unfortunately, this same crystalline polymorph is also generally the least soluble. In such cases it becomes desirable to develop formulations based on the amorphous form of the API, with stabilization obtained by the addition of precise combinations of additives. Polymers and other excipients are used in varying amounts to create stable formulations that retard the conversion of the more soluble amorphous API to its less soluble crystalline form. For purposes of optimization, these formulations are subjected to various stresses (temperature, humidity. etc.) to simulate accelerated aging while being monitored to ensure they remain amorphous, preserving their dissolution characteristics. Common techniques for analyzing the state of the API within a formulation include x-ray powder diffraction, birefringence, Raman microscopy and calorimetry. These techniques each exhibit their own trade-offs between sensitivity and selectivity, with X-ray diffraction generally considered the most powerful; detection limits down to 1-2% crystallinity are routinely observed. Polarized light microscopy (PLM) offers lower detection limits down to the single particle regime, however it lacks selectivity. All crystals, including excipient crystals will be detected with PLM making it not useful to analyze formulations in tablet dosage form.