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 [40].

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 [40].

Figure: different methods of LMWH preparation result in distinct chemical structures [41]

Enoxaparin Tinzaparin
Brand name Clexane
Manufacturing process Benzylation followed by alkaline hydrolysis Heparinase digestion
Mean molecular weight (daltons) 4500 6500
Elimination half-life (hours) 4.5 3.4
Bioavailability (%) 90–92 87
Anti-Xa/anti-IIa ratio 3.8 2.8
Anti-Xa activity (IU/mg) 100 100