Formulation and in-vitro evaluation of fast dissolving tablets containing a poorly soluble antipsychotic drug
Keywords:
olanzapine, ascorbic acid, co-amorphous dispersion, evaporation under vacuumAbstract
The aim of the present study was to formulate olanzapine fast dissolving tablets (FDT). Olanzapine is a poorly water soluble drug that undergoes first pass metabolism in liver resulted in low oral bioavailability. The water solubility is enhanced by formation of co-amorphous dispersion by solvent evaporation under vacuum method using a polycarboxylic acid (ascorbic acid) as a coformer in two different molar ratios (1:1 and 1:2). The prepared systems were evaluated using differential scanning calorimeter (DSC), Fourier Transform Infra-Red analysis (FTIR), X-ray powder diffraction (XRPD), Scanning electron microscopy (SEM) and saturated solubility. The co-amorphous dispersion system in a molar ratio 1:2 is higher in solubility than 1:1, so it was selected for incorporation into FDT formulation. Compatability study between olanzapine and different tablet excipients including DSC and FTIR showed that the drug is compatible with the selected tablet excipients. Direct compression method was used in FDT formulations using different types and concentrations of superdisintegrants. FDTs were evaluated for weight variation, hardness, friability, wetting time, drug content uniformity, invitro disintegration time and invitro dissolution study. All the prepared FDTs were complied with the compendia standards. F3 and F8 showed lower disintegration time and higher percent of drug dissolved, so they were selected for stability study. After storage for 3 months at 30ÀC at 65% relative humidity, both formulations were physically stable regarding color and integrity and had only minor increases in disintegration time, drug content and friability after three monthsÊ storage. The results indicate that olanzapine FDT tablets may serve as a successful strategy for enhancing the bioavailability of olanzapine.
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