Abstract
The aim of the study was to enhance solubility or dissolution characteristics of modafinil using its inclusion complexes (ICs) with β-cyclodextrin (β-CD) and hydroxypropyl β-cyclodextrin (HP β-CD). The phase solubility behavior of modafinil in the presence of various concentrations of hydrophilic carriers such as β-CD and HP β-CD (0.25-1.0% w/v) in distilled water was obtained at 37±2 °C. The solubility of modafinil increased with increasing the concentration of carriers. Gibbs free energy (G° tr) values were all negative, indicating the spontaneous nature of modafinil solubilization. Response surface modeling was used for development and data interpretation of the inclusion complexes. The ICs of modafinil with β-CD and HP β-CD were prepared at 1:0.5, 1:1,1:1.5 and 1:2 w/w ratio (Drug: Carrier) by kneading and physical mixing and found enhanced dissolution rate with increasing the carrier concentrations. Mean dissolution time (MDT) of modafinil decreased significantly after preparation of ICs by physical mixing and kneading. Host-guest interactions were characterized in solid state by Fourier-Transform Infrared Spectroscopy (FTIR). It was found that inclusion complex (IC) by kneading with β-CD at a 1:1 and HP β-CD with 1:0.5 weight ratio showed satisfactory enhancement of dissolution compared to pure drug. The XRD studies indicate the amorphous or microcrystalline states of modafinil in ICs. Significant improvement in solubility and dissolution of modafinil was observed with inclusion complex using two grades of cyclodextrins. The study suggested that HP β-CD complex of modafinil may be preferred over β-CD due to its result at half of the concentration when compared.
Keywords: Cyclodextrins, inclusion complexation, modafinil, response surface model, solubility and dissolution.
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