Comparative studies of the in vitro dissolution and in vivo pharmacokinetics for different formulation strategies (solid dispersion, micronization, and nanocrystals) for poorly water-soluble drugs: A case study for lacidipine

• Lacipil® had higher in vitro dissolution profiles than the micronized and nanonized tablets.
• Micronized and nanonized tablets showed improved oral bioavailability over Lacipil®.
• The in vitro dissolution study cannot mimic the in vivo process.

Different formulation strategies have been proposed for poorly water-soluble drugs. The objective of this study is to give an in vitro and in vivo comparison of a solid dispersion, micronization, and nanocrystals, with lacidipine as a model substance. Micronized lacidipine was obtained by jet milling, and nanocrystals were prepared by bead milling. The d50 for the microcrystals (11,200 nm) was about 20 times larger than that for nanocrystals (623 nm). Both colloidal dispersions maintained a crystalline state after milling. Lacipil®, lacidipine solid dispersion, was purchased from GlaxoSmithKline. It exhibited a much higher in vitro dissolution profile than both the micronized and nanonized tablets while the micronized and nanonized tablets showed approximately a 1.30- and 2.05-fold increase in AUC0–24 h compared with Lacipil®, respectively. Among the three formulation approaches, Lacipil® (solid dispersion) exhibited highest dissolution profile, while nanocrystals produced the greatest increase in oral bioavailability.

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