Table I: Tablet formulations of plain lovastatin (LVS), the physical mixture (PM), and complexes made with the coevaporation
(CPC) and the kneading methods (CPK).
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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 At fixed time intervals, 5-mL aliquots were withdrawn, filtered, suitably diluted, and assayed for LVS content by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.
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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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