Development of enoxaparin sodium polymeric microparticles for colon-specific delivery

BACKGROUND AND AIMS Recent studies have shown that low molecular weight heparins are effective in the treatment of inflammatory bowel disease. Therefore, there is considerable interest in the development of an oral colonic delivery pharmaceutical system allowing targeted release of heparin in the inflamed tissue. The objective of this study was to prepare microparticles for the oral administration and colonic release of enoxaparin and to evaluate the influence of certain formulation factors on their characteristics. METHODS Microparticles were prepared by water/oil/water double emulsion technique followed by solvent evaporation. The influence of several formulation factors on the characteristics of microparticles were evaluated. The formulation factors were alginate concentration in the inner aqueous phase, polymer (Eudragit(®) FS 30D and Eudragit(®) RS PO) concentration in the organic phase and ratios between the two polymers. The microparticles were characterized in terms of morphology, size, entrapment efficiency and enoxaparin release. RESULTS The results showed that increasing sodium alginate percentage reduced the encapsulation efficiency of enoxaparin and accelerated enoxaparin release. Regarding the influence of the two polymers, reducing polymer concentration in the organic phase led to a smaller size of microparticles, a lower entrapment efficiency and an important retardation of enoxaparin release. The formulation prepared with Eudragit(®) FS 30D limited the release to a maximum of 3% in gastric simulated environment, a specific characteristic of oral systems for colonic delivery, and fulfilled our objective to delay the release. CONCLUSIONS Microparticles prepared with Eudragit(®) FS 30D represent a suitable and potential oral system for the colonic delivery of enoxaparin.