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Published on: August 22, 2016
Oral delivery of low molecular weight heparin by polyaminomethacrylate coacervates
1Laboratory of Pharmaceutical Technology and Biopharmaceutics, University of Bonn, Bonn, Germany.
Purpose:
Oral bioavailability of low molecular weight heparin (LMWH) can be achieved by several advanced drug delivery approaches. Here, a new preparation method for coacervates (CAs) using non-toxic polyethylene glycol derivates was developed.
Methods:
LMWH were coacervated with polyaminomethacrylates (Eudragit® RL or RS) using polyethylene glycol (PEG) derivatives as non-toxic solvents. CAs were analyzed for their physicochemical properties and pharmacokinetic parameters were determined for different formulations in rabbits.
Results:
CAs from both polymer types using various PEGs were of irregular shape and had particle sizes of around 40 μm, encapsulation efficiencies of >90%, and complete LMWH in vitro release was obtained within 2 h. In vivo, oral Absorption at doses of 300 IU/kg was rather low (F < 2.5%) while dose increase resulted in a maximum at 600 IU/kg (FRL: 6.0 ± 1.2%; FRS: 5.8 ± 2.5%) and 1,200 IU/kg did not result in higher bioavailability (FRL: 4.6 ± 0.4%; FRS: 4.1 ± 0.8%). CAs were applicable to various LMWH types where the oral availability decreased in the order fondaparinux>enoxaparin>nadroparin>certoparin depending mainly on the molecular weight.
Conclusions:
CAs prepared by an organic solvent-free method allowed the oral delivery of LMWHs. The therapeutic efficiency and the simple and solvent-free manufacturing process underlines the high potential of this new preparation method.
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