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



Table V: Similarity factor for the release profiles of lovastatin in dissolution media-A (0.1 N HCl) (DM-A) and dissolution media-B (phosphate buffer [pH 6.8]) (DM-B).
Formulation studies. The kneading method was studied for physical properties to assess its tableting ability. The % compressibility and angle of repose of the complex prepared by the kneading method were 11.92% and 26.2, respectively, which indicate good compressibility and flow properties, thereby making the complex suitable for tableting. In general, compressibility index values up to 15% and an angle of repose between 25 and 30 results in good to excellent flow properties (38).

The release profile of LVS from tablets containing LVS without HPβ-CD and tablets containing LVS with HPβ-CD in both dissolution media is shown in Figure 9. During in vitro dissolution studies, the complex prepared by the kneading method exhibited approximately 95% and 85% drug release within 60 min from DM-A and DM-B, respectively. Tablets prepared by compressing the kneading method provided the same drug release within approximately 120 min. The t50% values of LVS also are significantly lowered in both the dissolution media.

The release of LVS from tablets made with the kneading method was faster and higher as compared with the tablets containing pure LVS and no HPβ-CD. Moreover, the hardness of all formulations is approximately the same, which indicates that improvement in the dissolution of LVS from tablets containing the complex made with the kneading method is not dependent on hardness. This confirmed the advantage of improved aqueous solubility of LVS in its complex form, which can be formulated as tablets with better dissolution characteristics. The release profiles of LVS from conventional tablets containing LVS are significantly different from tablets containing the complex made with the kneading method; the f2 values are 24.55 and 24.64 in DM-A and DM-B, respectively. The MDT values of LVS from tablets containing the complex made with kneading method in both dissolution media (46.02 min in DM-A and 55.64 min in DM-B) are significantly lower than that of conventional tablets containing only LVS and no HPβ-CD (87.96 min in DM-A and 92.96 min in DM-B).

Conclusion

This study showed a significant, linear increase in the aqueous solubility of lovastatin (LVS) with increasing concentrations of hydroxypropyl-β-cyclodextrin (HPβ-CD). The maximum studied concentration of HPβ-CD (14 mM/L) resulted in a 17.2-fold improvement in the saturation solubility of LVS. An inclusion complex of LVS and HPβ-CD in a molar ratio of 1:1 was prepared successfully with the kneading and coevaporation methods. The prepared complexes and the physical mixture of LVS and HPβ-CD were characterized by Fourier transform infrared, differential scanning calorimetry, and X-ray diffraction spectroscopy. When compared with the pure drug, the dissolution profile of the LVS and HPβ-CD complex is dramatically improved, which proved its suitability to develop an oral form. The inclusion complex prepared by the kneading method showed the highest improvement in in vitro drug release because of the presence of entrapped drug inside the HPβ-CD cavity. The absence of unentrapped drug also was well characterized by Fourier transform infrared, differential scanning calorimetry, and X-ray studies. The in vitro drug release of the physical mixture improved, too, but to a lesser extent compared with complexes prepared by the kneading and coevaporation methods. Tablets containing the complex prepared by the kneading method showed a better dissolution profile compared with tablets prepared using LVS without HPβ-CD. These findings suggested that LVS's poor dissolution profile can be overcome by preparing its inclusion complex with HPβ-CD.


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