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 IV: Mean dissolution time (MDT) values for pure lovastatin (LVS), the physical mixture (PM), and complexes prepared by the coevaporation (CPC) and kneading (CPK) methods in dissolution media-A (0.1 N HCl) (DM-A) and dissolution media-B (phosphate buffer [pH 6.8]) (DM-B).
The DP30 min (percent drug dissolved within 30 min) and t50% (time to dissolve 50% drug) values in 0.1 N HCl and the phosphate buffer (pH 6.8) are reported in Table III. (For ease in discussion, hereafter, abbreviations for 0.1 N HCl-dissolution media A [DM-A] and for phosphate buffer [pH 6.8]-dissolution media B [DM-B] are used.) From these data, it is evident that the onset of dissolution of pure LVS is very low in both dissolution media (DP30 min value 10.62% in DM-A and 13.75% in DM-B). Even t50% values in both dissolution media are much higher (>>3 h). The kneading and the coevaporation methods considerably enhanced DP30 min and lowered t50% values compared with pure LVS and the physical mixture. Figures 7 and 8 show the dissolution profiles of pure LVS, the physical mixture, and the complexes prepared by the coevaporation and the kneading methods in DM-A and DM-B, respectively, over a period of 3 h. It is evident that the dissolution rate of pure LVS is very low in both DM-A and DM-B: approximately 36.12% and 34.00% of the drug was dissolved in 3 h, respectively. The kneading method and the coevaporation method enhanced the dissolution rate of LVS significantly (90–100% in both dissolution media) within 3 h. Hence, the faster dissolution of LVS from the kneading method and the coevaporation method is attributed to the solubilizing effect of the carrier (HPβ-CD). In addition, other factors such as particle-size reduction, the absence of aggregation and agglomeration between hydrophobic drug particles, good wettability, and dispersibility of the dispersed drug (37) also might have contributed to the observed increase in the dissolution rate of LVS from complexes.


Figure 6: Wettability study of pure lovastatin, the physical mixture, and complexes prepared by the coevaporation and the kneading methods in water (tests performed in triplicate). CPK is the kneading method, CPC is the coevaporation method, PM is the physical mixure, and LVS is lovastatin.
The dissolution rate of LVS from the physical mixture is significantly higher (74.94% in DM-A and 78.37 % in DM-B) than that of pure LVS within 3 h. Physical mixing of LVS with HPβ-CD brings the drug in close contact with HPβ-CD. The increased dissolution rate observed in the case of the physical mixture may be caused by one or more of the factors mentioned previously.


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