Solubility Enhancement of Meloxicam Prepared via Binary and Ternary Phases Using Spray Congealing

Abstract

In this work, the utilization of a spray congealing technique was adopted to prepare enhanced release, solvent-free microparticles of meloxicam (Mel). The binary and ternary phases prepared by spray congealing with Polyethylene glycol 3000 (PEG-3) and Gelucire 44/14 (Gel-44) in different drug-to-polymer ratios were considered. The prevalent particle size (mean diameter) was in the range of 75-85 μm and the microparticles had good encapsulation efficiency up to 99.0 %. The formulations were characterized by solubilizing efficiency, physical properties, drug content and dissolution behavior. In addition, the anti-inflammatory activity was determined. The 
ternary system of Mel-PEG-Gel (T1, T2 and T3) was compared with those of the corresponding binary system of Mel-PEG (B1) or Mel-Gel (B2). Scanning electron microscope analysis showed that it was possible to obtain spherically shaped and non-aggregated  microparticles, with slightly drug crystals evident on the surfaces of drug-loaded microparticles. Differential scanning calorimetry and X–ray diffractometry were used to investigate the solid-state physical structure of the prepared microparticles. The results from X-ray diffraction and differential scanning calorimetry showed the absence of well-defined drug–polymer interactions. The solubility of inary 
phases (B1 or B2) was lower than the ternary phase's formulae (T1, T2 and T3). Consequently, the ternary phases as a carrier represents the most promising approach to the dissolution rate enhancement of meloxicam. From the in vitro release data, the selected formula prepared by spray congealing (T3) was enhanced the solubility and dissolution rate rather than other preparation techniques (physical mixture and solid dispersion by melting method). Finally, the microparticles prepared by spray congealing (T3) containing 10% Mel, 45% PEG-3 and 45% gelucire 14/44 exhibited higher anti-inflammatory activity on the paw edema of rats in comparison to the drug alone, physical mixture and solid dispersion.