Study of In Vitro and In Vivo Carbamazepine Release from Coarse and Nanometric Pharmaceutical Emulsions Obtained via Ultra-High-Pressure Homogenization

Once the coarse emulsions were prepared, 600 g measures were subjected to UHPH using a Nano DeBEE Laboratory Homogenizer (BEE international, South Easton, MA, USA), where the operating conditions employed were: zirconia nozzle (Z8) with an orifice diameter of 200 µm, six zirconia reactors with orifice diameter of 1.75 mm, a pressure of 3 × 104 psi (206.8 MPa), and a parallel flow configuration, with a total of four recirculation cycles. These conditions were previously defined by means of a series of tests conducted before the development of the nanoemulsions.

Abstract:
In the past decade, pharmaceutical nanotechnology has proven to be a promising alternative for improving the physicochemical and biopharmaceutical features for conventional pharmaceutical drug formulations. The goal of this study was to develop, characterize, and evaluate the in vitro and in vivo release of the model drug carbamazepine (CBZ) from two emulsified formulations with different droplet sizes (coarse and nanometric). Briefly, oil-in-water emulsions were developed using (i) Sacha inchi oil, ultrapure water, TweenTM 80, and SpanTM 80 as surfactants, (ii) methyl-paraben and propyl-paraben as preservatives, and (iii) CBZ as a nonpolar model drug. The coarse and nanometric emulsions were prepared by rotor–stator dispersion and ultra-high-pressure homogenization (UHPH), respectively. The in vitro drug release studies were conducted by dialysis, whereas the in vivo drug release was evaluated in New Zealand breed rabbits. The results showed that nanoemulsions were physically more stable than coarse emulsions, and that CBZ had a very low release for in vitro determination (<2%), and a release of 20% in the in vivo study. However, it was found that nanoemulsions could significantly increase drug absorption time from 12 h to 45 min.