(380t) Imiquimod Particle Formation Using the Supercritical Antisolvent (SAS) Process

One of the main problems emerging from the pharmaceutical industry is the low solubility of hydrophobic drugs, which can cause insufficient bioavailability. Thus, approaches able to improve the solubility of these drugs are of high interest. An alternative to this problem is the use of supercritical fluid micronization, a particle formation method, which has large potential to be used in the pharmaceutical field because of its low toxicity, low cost and relatively mild processing conditions, since carbon dioxide is one of the most common antisolvents used for this purpose. In the present study, imiquimod, a topical chemotherapeutic used to treat skin tumors such as basal cell carcinoma, anogenital warts, and keratosis, was processed using the supercritical anti-solvent (SAS) technique aiming at improving its solubility in aqueous media. This drug has poor solubility in apolar solvents and is soluble only in acidic aqueous solutions. Thus, glacial acetic acid was chosen as solvent. The processing conditions used were 120 bar, 60°C, CO₂ flow rate of 15 g/min and a solution flow rate of 0.5 mL/min. The characterization of the material obtained was performed by X-Ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). It was possible to produce particles with a thin, porous, sheet-shape d structure that was quite different from the untreated drug, as observed by SEM analysis. The FTIR analysis showed that the functional groups were maintained, ensuring that the drug has not been degraded. TGA and DSC analysis showed that the drug degrades only at 300°C. Thus, the supercritical antisolvent process was adequate to produce particles with high surface area and with preserved drug structure.

The authors are grateful for the financial support of this work by the São Paulo Research Foundation (FAPESP) and the National Council for Scientific and Technological Development (CNPq), both from Brazil