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


The MDT value of LVS from pure LVS, the physical mixture, and complexes prepared by the coevaporation and the kneading methods were calculated (n = 3) using the equation:












Figure 7: In vitro dissolution profiles of pure lovastatin and its physical mixture and complexes in dissolution media-A (0.1 N HCl) (tests performed in triplicate). CPK is the kneading method, CPC is the co-evaporation method, PM is the physical mixure, and LVS is lovastatin.
in which i cr, n is the number of dissolution times, tmid is the time at the midpoint between times ti and ti–1, and ΔM is the amount of LVS dissolved (μg) between times ti and t i–1. The obtained values of MDT for pure LVS, the physical mixture, and complexes prepared by the coevaporation and the kneading method are presented in Table IV. MDT reflects the time for the drug to dissolve and is the first statistical moment for the cumulative dissolution process that provides an accurate drug-release rate (17). It is an accurate expression for drug-release rate. A higher MDT value indicates greater drug-retarding ability (18). The MDTs of LVS are 64.92 min in DM-A and 66.13 min in DM-B. These values decreased a greater extent after the preparation of a complex of LVS with HPβ-CD (e.g., 22.00 min in DM-A and 30.56 min in DM-B for the kneading method and 33.79 min in DM-A and 41.08 min in DM-B for the coevaporation method). The physical mixture also shows sufficiently lower MDT value compared with pure LVS in both dissolution media. The kneading method, which exhibited the best dissolution profile, was used for the formulation studies.


Table III: The % drug dissolved within 30 minutes (DP30 min) and the time to dissolve 50% of the drug (t50%) from pure lovastatin (LVS), the physical mixture (PM), and complexes made with the coevaporation (CPC) and the kneading methods (CPK) in DM-A* and DM-B**.
A value of 100% for the similarity factor (f2) suggests that the test and reference profiles are identical. Values between 50 and 100 indicate that the dissolution profiles are similar, whereas smaller values imply an increase in dissimilarity between release profiles (14). Calculated f2 values are presented in Table V. From this table, it is evident that the release profile of LVS prepared by the kneading method is very different from pure LVS in both dissolution media (f2 values 10.55 in DM-A and 11.64 in DM-B). Even release profiles of LVS prepared by the coevaporation method and the physical mixture also are significantly different from pure LVS in both dissolution media.


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