In this research, the dissolution rate of poorly water-soluble cilostazol (CLT) was improved by adsorbing drug solution onto the surface of carriers, followed by solvent evaporation. Various kinds of excipients as well as different drug-carrier ratios were examined to define the optimal condition for adsorption process. The optimized adsorbent system was developed into immediate release (IR) tablets by wet granulation method. The drug release profiles of various formulations were assessed by in vitro dissolution testing in intestinal fluid (pH 6.8) containing sodium lauryl sulfate 0.2%. To elucidate the mechanism of dissolution enhancement, differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), fourier transform infrared spectroscopy (FT-IR) and field-emission scanning electron microscope (FE-SEM) were simultaneously employed. The result proved that the adsorption mixtures of CLT with Aerosil 300 and lactose monohydrate provided better drug dissolution rate compared to mannitol-containing sample. In both cases of Aerosil and lactose monohydrate, 1:2 and 1:4 ratios presented nearly similar release profiles which were markedly higher than 1:1 ratio. Drug-carrier ratio of 1:2 with sufficient carrier surface area was then selected for formulation development. Aerosil-based adsorption powders could not be compressed into tablet due to low compressibility. Therefore, CLT-loaded tablets were prepared based on the adsorbent system of lactose monohydrate. The resulting tablets displayed almost complete drug release within 90 minutes which was significantly higher than control tablet as well as the commercial product Pletaal® (Otsuka) which contained hammer-milled CLT with mean particle size approximately 13 µm. DSC and PXRD thermograms indicated that the crystalline property of CLT remained in adsorption sample with diminutive peak intensity. FT-IR spectra assumed that the hydrogen bond was formed between drug molecule and lactose monohydrate. SEM analysis confirmed that CLT crystals with reduced size around 10 µm were adsorbed onto adsorbent material surface. This adsorption method is a promising strategy to improve the dissolution rate of poorly water-soluble drugs.
