Production of Eudragit/ampicillin Microparticles by Supercritical Antisolvent Coprecipitation

Abstract

In this paper, the supercritical antisolvent (SAS) technique was proposed to coprecipitate ampicillin sodium (AMPI), an antibiotic chosen as the model drug, by using Eudragit L100-55 as the polymeric carrier. In the last years, supercritical carbon dioxide (scCO2) based techniques were frequently used to produce active principle/biopolymer composites with fast or controlled drug release. In this work, the Eudragit L100-55 micronization was studied and, as desired, the attainment of spherical microparticles of polymer with mean size in the range 1.64 - 1.99 µm was achieved. Then, SAS coprecipitation Eudragit/AMPI was investigated to verify the potential of Eudragit as the carrier for drug controlled delivery. Working at the best operating conditions, in terms of pressure (100 bar) and of overall concentration in the liquid solution (50 mg/mLDMSO), microspheres Eudragit/AMPI 20/1 and 10/1 w/w were obtained, with mean diameters of 2.52 µm and 1.53 µm, respectively. Release studies showed that the dissolution rate of ampicillin was prolonged 4 and 3 times, respectively in the case of SAS coprecipitated powders at 20/1 and 10/1 ratios. This outcome allowed to reduce the frequency of administration up to once a day, with fewer side effects due to antibiotic overdosing.