Encapsulation of low molecular weight heparins: Influence on the anti-Xa/anti-IIa ratio

Tinzaparin and nadroparin, two low molecular weight heparins (LMWH), were encapsulated within microparticles by the double emulsion method using ammonium methacrylate copolymer (Eudragit® RS) alone or mixed with poly (d,l-lactic-co-glycolic acid) at different ratios.The resulting microparticles were characterized in vitro according to particle size, encapsulation rate and release profiles both by chemical and biological methods. The biological method was based on the measurement of the anti-Xa/anti-IIa ratio typical of each LMWH. This ratio also reflects the relative proportion between active chains below and above the critical chain length of 5000 Da (i.e. BCL and ACL chains), since LMWH are mixtures of chains with various lengths and activities.For both LMWH, high entrapment efficiencies, expressed as anti-Xa and anti-IIa activities, were obtained and amounted to anti-Xa/anti-IIa ratios close to the commercial ratio. During the in vitro release, whatever the formulation, more BCL chains were released than ACL chains: a higher (compared to commercial ratio) and stable anti-Xa/anti-IIa ratio was observed. This increase of the anti-Xa/anti-IIa ratio was influenced by the type of LMWH used and the composition of the Eudragit® RS formulation. This type of microparticles could constitute a new pharmaceutical form of LMWH with a higher anti-Xa/anti-IIa ratio than commercial forms.

LMWH-loaded microparticles prepared by double emulsion method allowed an increase of the characteristic LMWH anti-Xa/anti-IIa ratio during the in vitro release and may, in this way, potentially lead to a new pharmaceutical form of LMWH.Figure optionsDownload as PowerPoint slide