Drug Candidates

Current knowledge suggests that adsorption on OMS can enhance and control dissolution rate of a wide variety of compounds. However, the number of in vivo studies using drugs incorporating OMS technology remains limited. Although release has been suggested to be pH-independent [44], the fate of released drug is not, and for most poorly soluble drugs, precipitation following release is likely. Thus, the in vivo performance of OMS may depend not only on the release rate, but also (and even more so) on the rate and extent of drug precipitation following release.

Mellaerts et al. compared the biopharmaceutical performance of OMS loaded with the poorly soluble weak base itraconazole [10], against that of the commercial solid dispersion product, Sporanox. In rabbits and dogs, there were no statistically significant differences in terms of rate and extent of absorption between the OMS formulation and Sporanox (Fig. 10.5).

In a subsequent study in rats, Van Speybroeck et al. demonstrated that the performance of the OMS-itraconazole formulation was enhanced by coadminister-ing the polymeric precipitation inhibitor hydroxypropyl methylcellulose [35].

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w la 50

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10 15

hydroxyitraconazole

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10 15

Fig. 10.5 Plasma concentration-time profiles of itraconazole and its major active metabolite hydroxyitraconazole in rabbits, after administration of crystalline drug (open triangle), an SBA-15-based formulation (filled diamond), and Sporanox (open square)

10 15

Fig. 10.5 Plasma concentration-time profiles of itraconazole and its major active metabolite hydroxyitraconazole in rabbits, after administration of crystalline drug (open triangle), an SBA-15-based formulation (filled diamond), and Sporanox (open square)

Fig. 10.6 Schematic illustrating the effect of HPMC addition on the biopharmaceutical performance of SBA-15

This polymeric component improved absorption by inhibiting itraconazole precipitation in the small intestine. Figure 10.6 illustrates this effect.

Fenofibrate, another poorly soluble compound has also been evaluated in vivo (rats) as described in Sect. 10.2.2, where enhanced absorption was ascribed to stabilization of released drug as supersaturated solution [23].

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