Enhancement of Solubility and Dissolution Rate of Trandolapril Sustained Release Matrix Tablets by Liquisolid Compact Approach

Abstract

Trandolapril (TLP), is an antihypertensive agent, administered orally. It is having low oral bioavailability (4–9%) due to poor aqueous solubility, it undergoes CYP3A4 mediated hepatic first-pass metabolism. Liquisolid compact (LSC), the technique has the potential to improve the oral bioavailability by increasing solubility and dissolution rate of poorly water-soluble drugs. In the present work, TLP LSCs were prepared with polyethylene glycol-400 as a vehicle, Avicel, Neusilin as carriers and Aerosil as coating material. LSC and sustained release tablets of LSC containing hydroxypropyl methylcellulose K15M polymer, were prepared by direct compression method and characterized for hardness, friability, drug content and in vitro release studies in pH 6.8 phosphate buffer for LSC and 0N HCl for 2 h followed by pH 6.8 phosphate buffer for subsequent hours for SR LSC, using USP type-1 apparatus. Solid state characterization of TLP and TLP-LSC was examined using differential scanning calorimeter (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM) studies. Physical parameters of the prepared LSC tablets were found to be within the acceptable limits. In vitro dissolution studies of optimized SR LSC (F3) formulation had shown sustained drug release of 97.3 ± 2.59% in 14 h with Peppas model (r2 = 0.981) followed by non-Fickian diffusion (n = 0.659) mechanism, whereas LSC tablets showed 94.1 ± 3.11% drug release in 120 min. DSC and XRD analysis indicated that TLP was amorphous form in LSC mixture. SEM studies revealed that TLP was adsorbed onto the surface of carrier material compared with the pure drug having needle-shaped crystal lattice. Therefore, LSC technique can improve the solubility and dissolution rate of poorly water-soluble drug such as TLP.