Over the past two decades increasing attention has been focused on solid-state chemistry of pharmaceuticals because the selection of solids with suitable physicochemical properties is a key factor within pharmaceutical development strategies (York, 1999). Recently, a new approach using supercritical fluids for particle design of pharmaceutical materials is being actively pursued due to its major advantages over conventional pharmaceutical processing such as high purity of products, ability to control particle size and narrow particle size distribution, single step process and free from residual solvent. Among these advantages, one of the major challenges is to improve bioavailability and stability of poorly soluble active pharmaceutical ingredient (API) using supercritical fluids particle design technology (Majerik, 2007). Therefore, the aim of this work is to investigate the influence of co-precipitation of API and excipient using supercritical anti-solvent (SAS) process. The API-excipient composites were generated by varying process conditions such as API-excipient ratios, relative flow rates of supercritical carbon dioxide and API solution, pressure and types of solvent. Besides that, stress test on SAS powders were carried out at 75% RH and room temperature in order to evaluate its physical stability. The untreated and SAS powders (after and before storage) were characterized using scanning electron microscopy (SEM, morphology), powder X-ray diffractometry (PXRD, crystallinity), dynamic vapor sorption (DVS, sorption isotherm) and differential scanning calorimetry, (DSC, crystallinity, Tm and ΔHf).

Our preliminary results revealed that it was technically feasible to generate a fully X-ray amorphous SAS API-excipients co-precipitated powders, which remained amorphous after 1-week storage at 75% RH and room temperature. The amorphous content of the SAS co-precipitated products were influenced by the API-excipients compositions. Besides that, different morphologies of SAS powders were obtained as compared to the untreated powders.

References:

1. York, P., Strategies for particle design using supercritical fluid technologies, PSST, 2 (1999), 430-440

2. Majerik, V., Charbit, G., Badens, E., Horvath, G., Szokonya, L., Bosc, N., and Teillaud, E., Bioavailability enhancement of an active substance by supercritical anti-solvent precipitation, J. Supercrit. Fluids, 40 (2007), 101-110