Figure 2: The phase solubility curve of lovastatin in an aqueous solution of hydroxypropyl-β-cyclodextrin (HP-βCD) at 37 8C.
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Tablets containing 10 mg of LVS were made by direct compression using various formulation excipients such as directly compressible
lactose, colloidal silicon dioxide, and magnesium stearate (see Table I). Tablets equivalent to 10 mg LVS were made similarly
using the kneading method, but using less lactose. The blend was compressed on an eight-station, single-rotary machine (Cadmach,
India) using round-shaped, flat punches to obtain tablets of 4–7 kg/cm2 hardness and 3.5–3.7 mm thickness (see Table I). For the assay, three tablets were crushed and a blend equivalent to 10
mg of LVS was weighed and dissolved in dissolution mediums. The tablets were studied in triplicate (n = 3) for the drug-release profile using the same methodology described for the in vitro dissolution studies.
Statistical analysis. A model-independent, mathematical approach proposed by Moore and Flanner (14) for calculating f2 was used for comparison among the dissolution profiles of various samples. The f2 is a measure of similarity in the percentage dissolution between two dissolution curves and is defined by following equation:
in which n is the number of withdrawal points, Rt is the percentage dissolved of reference at the time point t, and Tt is the percentage dissolved of test at the time point t (14).
A value of 100% for 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).
Results and discussion
Phase-solubility study. Phase-solubility analysis has been among the preliminary requirements for the optimization of the development into inclusion
complexes of the drugs as it permits an evaluation of the affinity between β-CD and drug molecule in water. This process has
been used by many researchers to determine the exact molar ratios in which the drugs could make complexes with β-CD (23, 24).
The solubility of LVS in water at 25 °C is 0.4 g/mL; therefore, LVS can be considered a water-insoluble drug. The phase-solubility
diagram of LVS in the presence of HPβ-CD was obtained by plotting the apparent equilibrium concentration of LVS against various
molar concentrations of HPβ-CD (see Figure 2). This representation provides direct information about the complexation efficiency.
The apparent solubility of LVS increased linearly as a function of HPβ-CD concentration over the entire concentration range
studied. The solubility of LVS is increased 17.2-fold at a 14 mM/L concentration of HPβ-CD. Increased solubility may be caused
by improved dissolution of LVS particles in water by HPβ-CD.
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