Pellets for oral administration of low-molecular-weight heparin.
BACKGROUND
Oral absorption of low-molecular-weight heparin (LMWH) is limited by its molecular size and negative charge. It has been shown previously that orally administered polymeric nano- or microparticles containing encapsulated LMWH have led to gastrointestinal absorption of heparin in rabbits.


METHODS
Based on these investigations, pellets containing two LMWHs, enoxaparin (MW 4500 Da) or bemiparin (MW 3600 Da), and EudragitRS30D (ERS), were prepared using extrusion/ spheronization technique. Uncoated or coated (ERS) pellets were evaluated in vitro and in vivo on rabbits.


RESULTS
Enoxaparin pellets showed fast in vitro release in phosphate buffer (pH 7.4) and prolonged in vivo drug absorption after a single oral dose of 600 anti-Xa IU/ kg of body weight, leading to relative bioavailabilities ranging from 9.7 +/- 1.9% to 12.8 +/- 2.7% and anti-Xa activity over the curative dose. Bemiparin included in matrix pellets of ERS and coated with ERS exhibited in vitro prolonged release up to 4 hours and in vivo anti-Xa activity below the therapeutic minimum value of 0.1 IU/mL.


CONCLUSIONS
This study presents LMWH in a pellet dosage form, which compared to nano- or microparticles, may offer a more convenient and industrializable way of manufacture leading to an easier scale-up process.
Scala-Bertola
Julien
J
Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, University Henri Poincaré, Nancy, France.
Gajdziok
Jan
J
Rabisková
Miloslava
M
Bonneaux
François
F
Lecompte
Thomas
T
Sapin
Anne
A
Maincent
Philippe
P
D000180:Acrylic Resins / Q000737:chemistry; D000284:Administration, Oral; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage*; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics; D017984:Enoxaparin / Q000008:administration & dosage; D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D055595:Mechanical Phenomena; D010316:Particle Size; D010592:Pharmaceutic Aids / Q000737:chemistry; D011817:Rabbits; D012995:Solubility; D013997:Time Factors
D000180:Acrylic Resins; D000925:Anticoagulants; D003692:Delayed-Action Preparations; D017984:Enoxaparin; D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight; D010592:Pharmaceutic Aids; C050528:Eudragit RS; C411345:bemiparin