Solid-State Characterization and Dissolution Properties of Lovastatin Hydroxypropyl-β-Cyclodextrin Inclusion Complex - Pharmaceutical Technology

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Solid-State Characterization and Dissolution Properties of Lovastatin Hydroxypropyl-β-Cyclodextrin Inclusion Complex
The objectives of this study were to prepare and characterize inclusion complexes of lovastatin with hydroxypropyl-β-cyclodextrin (HPβ-CD) and to study the effect of the complexes on the dissolution rate of lovastatin (LVS). The findings suggest that LVS's poor dissolution profile can be overcome by preparing its inclusion complex with HPβ-CD.

Pharmaceutical Technology

Figure 8: In vitro dissolution profiles of pure lovastatin and its physical mixture and complexes in dissolution media-B (phosphate buffer [pH 6.8]) (tests were done in triplicate). CPK is the kneading method, CPC is the coevaporation method, PM is the physical mixure, and LVS is lovastatin.
The improvement in wettability of LVS by the physical mixture, the kneading method, and the coevaporation method is shown in Figure 6. The kneading method and the coevaporation method showed highest wettability in water (99.82% and 90.04%, respectively), as compared with plain LVS (31.88%). Even the physical mixture of HPβ-CD with LVS enhances the wettability of LVS in water significantly. The % porosity of LVS, the physical mixture, and complexes prepared by the coevaporation and the kneading methods were 0.54 (0.02), 0.72 (0.08), 0.98 (0.06), and 1.03 (0.07), which ruled out a possible improvement in wettability because of variation in the samples' porosity.

Figure 9: Comparative drug-release profiles of conventional tablets containing lovastatin (LVS) and tablets containing a complex made with the kneading method (CPK) in dissolution media-A (0.1 N HCl) and dissolution media-B (phosphate buffer [pH 6.8]) (tests performed in triplicate).
It is generally accepted that the dissolution media are not completely representative of gastrointestinal conditions, yet it is proposed in guidelines that a good method will use a dissolution media that is physiologically meaningful or closely mimics in vivo conditions (30, 31). It has been suggested that the inclusion of surface active agents in dissolution media is important for poorly soluble compounds because the lack of surface tension-lowering agents would result in poorer wetting and in vitro dissolution rates that are not representative of in vivo rates (32). FDA has promoted the use of surfactants in media for conducting dissolution studies of poorly soluble compounds (33, 34).

Dissolution studies of pure LVS and all other prepared systems (complexes and physical mixture) were carried out in dissolution media (0.1 N HCl and phosphate buffer pH 6.8) containing aqueous sodium lauryl sulfate solution (0.25% w/v) because sodium lauryl sulfate showed minimal surface tension at 0.2% with no significant change at higher concentrations (35, 36). When the LVS was dispersed on the surface of the aqueous surfactant solution, LVS rapidly left the surface and was dispersed in the bulk of solution, which indicates wetting of LVS, unlike pure water.


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