## 4 Discussion  
Glibenclamide (Gly) and lipoic acid (LA)are often co-administered as separate pharmaceutical forms, this association targeting lowering blood glucose levels and managing diabetic neuropathy, together with other benefits. Consequently, the development of innovative multi-components dosage forms presents a significant interest.  
New polymeric system-type microparticles based on chitosan (CS) were obtained, in which Gly and LA were included in the matrix.  
The analysis of the results evidenced that EE% and DL% of the active substances (Gly, LA) into the CS matrix are dependent on the characteristic of the active substances in terms of molecular weight and hydrophilic-lipophilic balance. For LA, which has a pronounced hydrophilic character and low molecular weight, EE% was 35.84% for the CS-LA microparticles, and 39.68% for the CS-Gly-LA microparticles.Related to Gly, a substance with pronounced lipophilic character and higher molecular weight, EE% was significantly higher, 97.91% for the CS-Gly microparticles, and 94.66% for CS-Gly-LA microparticles, respectively. So, it could be appreciated that the low molecular weight and hydrophilic character facilitate the release of LA from the polymer matrix, while the higher molecular weight and lipophilic character favor the retention of Gly into the polymer matrix. In addition to this, the favorable influence of the association of Gly and LA in the same polymeric matrix on the entrapment efficiency of LA can be noticed; the EE% of LA increased from 35.84% in CS-LA microparticles to 39.68% in CS-Gly-LA microparticles. At the same time, the EE% of Gly decreased insignificantly, from 97.91% to 94.66%. These data support the benefit of including both active substances into the CS matrix, CS-Gly-LA microparticles presenting the theoretical premises for a multi-target treatment of diabetes mellitus.  
Pertainingto the swelling degree (SD%), the results highlight that the encapsulation of the active substances (Gly, LA) into the polymeric matrix was associated with decreasing of the swelling degree, both in distilled water and in SGF. It was also noted the SD% in SGF was higher than in distilled water, and the thermodynamic equilibrium was reached earlier (after 90 min, compared to 120 min for distilled water). These data support a better behavior in SGF than in distilled water, which could be beneficial for microparticle behavior in physiological gastrointestinal media.  
The polymeric systems were formulated for oral administration, this route being more acceptable for patients. The kinetic release of the active substances is an important step in the characterization  
Figure 9: Releasing percent (%) from CS-Gly–LA system.  
of the polymeric systems, being a landmark for in vivo behavior of the systems developed. From the obtained results (Figures 8 and 9), the releasing percent as function of time, it can be observed that the release of the active substances from the polymeric matrix followed a different kinetic, depending on their hydrophilic-lipophilic balance. The results reveal the favorable influence of the LA on the release of Gly from the chitosan matrix, the releasing percent for Gly being 52.49% from CS-Gly microparticles, and 75.17% from CS-Gly-LA microparticles.