Strategy ASynthesis of PolyLLlactide Microspheres Loaded with Omeprasol [50

Omeprasol (5-methoxy-2-{[(4-methoxy-3,5-dimethyl-2-pirydyl)-methyl]-sulfi-nyl}-1H-benzimidazole) (structure shown in Fig. 24), known as an inhibitor of an enzyme (H + -K + )ATPase [66,67], has been used as a model drug. Polymerization of l,l-lactide was prepared and initiated according to description given in Section IV.B. Initial monomer, initiator (stannous octoate), and poly(dodecyl acrylate)-g-poly(e-caprolactone) were equal to 2.5 x 10-1 mol/L, 4.6 x 10-3 mol/L and 1.6 x 10-1 g/L, respectively. Polymerization was carried out at 95°C. When polymerizing mixture became turbid, i.e., when microspheres were nucle-

Omeprasol FIG. 24 Chemical structure of omeprasol.

ated, solution of omeprasol in heptane was added dropwise. Final concentration of omeprasol in polymerizing mixture was 5 x 10-3 mol/L. Polymerization was carried out for 2 h and afterward microspheres were isolated in the usual way (cf. Section IV.B). The SEM image of these microspheres is shown in Fig. 25. The number average diameter (Dn) and diameter polydispersity index (Dw/Dn) were 1.73 pm and 1.17, respectively.

It has been found that omeprasol was simply entrapped in microspheres without being bound chemically. In GPC traces of dissolved microspheres the signals of poly(l,l-lactide) and omeprasol gave isolated peaks (cf. Fig. 26). It is important to note also that in the 1H NMR spectrum of poly(l,l-lactide)/omepra-sol microspheres only signals of polyester and drug were present, suggesting

FIG. 25 SEM image of poly(l,l-lactide/omeprasol) microspheres. (From Ref. 50.)

0.20

25 30 35

Elution volume, nil

FIG. 26 GPC trace of poly(l,l-lactide)/omeprasol microspheres in THF. (From Ref. 50.)

absence of any side products (cf. Fig. 27). On the basis of UV spectra of po-ly(l,l-lactide)/omeprasol microspheres dissolved in THF, loading was found equal to 11 wt %.

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