In vitro kinetic release study of ketoprofen enantiomers from alginate metal complexes

Abstract

Background To explore the release behavior of ketoprofen enantiomers from alginate-metal-complexes. Five mathematical models of drug release kinetics were investigated. Results Beads of alginate-metal complexes, loaded with racemic ketoprofen, were prepared by the ionotropic method. Divalent (Ca, Ba, Zn) and trivalent (Fe, Al) metals were used in the preparation of single-metal and mixed-metal alginate complexes. In vitro release experiments were carried out in an aqueous phosphate buffer medium at pH = 7.4. The concentrations of ketoprofen released enantiomers were determined using chiral HPLC technique. The obtained data were used to simulate the release kinetic of ketoprofen enantiomers using various mathematical models. The Korsmeyer-Peppas model was the best fit for Ca, Al, and Fe beads. Moreover, alginate-iron beads tend to release the drug faster than all other cases. In contrast, the drug release for alginate-barium complex was the slowest. The presence of barium in alginate mixed-metal complexes reduced ketoprofen release in the case of Fe and Zn, while it increased the release in the case of Al complex. Conclusion In all the studied cases, ketoprofen showed very slow release for both enantiomers over a period exceeded 5 h (10 days in some cases). The release rate modification is possible using different multivalent metals, and it is also feasible by using two different metals for congealing either consecutively or simultaneously.

Alginate Metal Complexes and Their Application

“…On the other hand, the kinetic simulation of studied beads [63,64] shows that the best fit models for each enantiomer and the racemic mixture were the same. However, the obtained models differ depending on the type of complexation due to the resulting "egg-box" structure.…”

“…Our previous studies were among the first publications in this field [62][63][64]. Alginate metal complexes in form of beads were prepared by the ionotropic gelation method.…”

“…In all cases, the resulted beads were characterized; bead size, metal content, shrinkage ratio, drug loading, and loading efficiency were calculated. The in-vitro release was carried out in an aqueous phosphate buffer that resembles gastric medium (6.8-7.4), and the enantioselective release (ESR) was observed in many complexes [62][63][64].…”

“…Racemic ketoprofen was dissolved with sodium alginate in phosphate buffer solution (PBS, pH = 7.4). The final ratio was 1 to 3.75 (w/w) [62][63][64]. The congealing solution contained a metal chloride (3% w/v) at room temperature.…”

“…Beads were separated and dried at 40°C for 48 h, the method was described in detail in Refs. [62][63][64]. However, beads were released in PBS with pH = 7.4.…”