(398ak) Production of Nano/Micro Particles of Antiretroviral Drugs Using Supercritical Technology

An important demand in the pharmaceutical industry is the production of bioactive particles with well-defined morphology and reduced size in order to increase the bioavailability of the drug in the body. This makes it possible to reduce the need for daily drug intake with consequent reduction of side effects to the patient. One can also increase the circulation time of drug in the body, so as to increase the efficiency of the therapy. Since the particle size distribution of the drug may affect its pharmacological action, it is desirable that it has the lowest size distribution.

Various techniques are used to achieve these objectives in the formation of particles, such as spray-drying, freeze-drying and granulation, among others, which require drastic conditions of operation and may not allow control of the size of the drug particles formed. As an alternative to the limitations imposed by conventional techniques, supercritical technologies have been used in micronization of bioactive particles, producing particles of defined morphology and small size distribution. These technologies utilize a fluid in supercritical conditions, usually carbon dioxide, because of their low toxicity and high diffusion coefficient. Its use is fairly stated in micronization of labile substances, since its critical point is considered mild. The supercritical technologies have the advantage of easy control of particle characteristics with small variations in operating conditions such as pressure and temperature. In addition, the formed particles tend to have low residual solvent quantity than those formed by traditional techniques and a lower number of separation processes in order to obtain the final product.

Various techniques for the production of particles using supercritical technology where carbon dioxide can act as a solvent, as in the Rapid Expansion of Supercritical Solutions (RESS) or anti-solvent techniques such as Supercritical AntiSolvent (SAS) and Solution-Enhanced Dispersion by Supercritical Fluids (SEDS). The application of the technique depends on the drug solubility in the supercritical fluid.

The SAS technique, used in this work, is used in micronization of drugs with low solubility in supercritical media. Thus, the bioactive substances are solubilized in an organic solvent soluble in the supercritical fluid. The fluid is injected into a vessel and expands, while the organic solution containing the drug is also injected into the same vessel. Carbon dioxide removes the organic solvent, promoting supersaturation of the drug in the middle and causing precipitation. The SAS technique has proved effective not only in micronization of drugs, but also in the synthesis of drug delivery systems and encapsulation of bioactive compounds in various substances.

There are several factors that affect the size of the particles obtained, their size distribution and morphology. In this work will be tested different operating conditions in micronization of antiretroviral drugs such as temperature, pressure, concentration and solution flow drug/solvent, among others. The organic solvent used to solubilize the drug is acetone.

It is expected thereby producing nano and micrometric particles through the SAS technique to improve the bioavailability of drugs in the body and to study the influence of various operational parameters on the characteristics of the produced particles.