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 I: Tablet formulations of plain lovastatin (LVS), the physical mixture (PM), and complexes made with the coevaporation (CPC) and the kneading methods (CPK).
Dissolution studies of LVS in powder form, the physical mixture, and complexes prepared by the coevaporation and the kneading methods were performed to evaluate the in vitro drug-release profile. Dissolution studies were carried out using a USP dissolution apparatus type II with a 500-mL dissolution medium at 37 C 0.5 C and 50 rpm for 3 h. In addition, 0.1 N HCl and a phosphate buffer (pH 6.8) containing 0.25% (weight/volune [w/v]) of sodium lauryl sulfate were used as other dissolution mediums. At fixed time intervals, 5-mL aliquots were withdrawn, filtered, suitably diluted, and assayed for LVS content by measuring the absorbance at 238.2 nm using a spectrophotometer. An equal volume of fresh medium at the same temperature was placed into the dissolution medium after each sampling to maintain its constant volume throughout the test.

Pure drug, the physical mixture, and complexes prepared by the coevaporation and the kneading methods were evaluated in dissolution-rate studies. Dissolution studies were performed in triplicate (n = 3) and the calculated mean values of cumulative drug release were used while plotting the release curves. MDT values were calculated to compare the extent of improvement in the dissolution rate of the physical mixture, and the complexes prepared by the coevaporation and the kneading methods. Preliminary tests demonstrated that there was no change in the λmax of LVS because of the presence of HPβ-CD dissolved in the dissolution medium.


Table II: Gibbs free energy of transfer (ΔGtr) for the solubilization process of lovastatin in aqueous solutions of hydroxypropyl-β-cyclodextrin (HP-βCD) at 37 8C.



Formulation studies. Formulation excipients were selected on the basis of preliminary tests that demonstrated the excipients did not interfere with the λmax of LVS. The % compressibility and the angle of repose were measured to assess the tableting ability of the kneading method.

The % compressibility was calculated using the following equation:











in which V0 is the powder volume before tapping and Vf is powder volume after tapping infinitely. The powder volume was calculated from Kawakita's equation (21) using data from 200 tapping points obtained with a tapping density analyzer (bulk density test apparatus, DBK Instruments, Mumbai, India) equipped with a 20-mL cylinder.

For the angle of repose measurement, a pile of powder was carefully made by dropping the powder material through a funnel tip from a height of 2 cm (22). The angle of repose was calculated by tangentially inverting the ratio of the formed pile's height and radius.


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