Production Process

LMWHs are a diverse group of chemically distinct compounds. Most are prepared by various chemical or physical depolymerisation techniques; others, such as tinzaparin, are produced by enzymatic depolymerisation [47].

Clexane® is obtained by chemical β elimination of the benzyl ester of heparin derived from porcine intestinal mucosa. Each LMWH is manufactured using a slightly different method, conferring unique properties on each product. As a result of these differences in manufacturing techniques, the available products differ markedly in terms of their mean molecular weights, mix of polysaccharide chain lengths, and pharmacological properties [47].

Pharmacological properties of LMWH
Enoxaparin Dalteparin Tinzaparin
Brand name Clexane Fragmin Innohep
Manufacturing process Benzylation followed by alkaline hydrolysis Controlled nitrous acid depolymerisation Heparinase digestion
Mean molecular weight (daltons) 4500 6000 6500
Elimination half-life (hours) 4.5 3–5 3.4
Bioavailability (%)90–92 87 87
Anti-Xa/anti-IIa ratio 3.8 2.7 2.8
Anti-Xa activity (IU/mg) 100 156 100