TY - JOUR AU - Thakkar, Hetal P. AU - Desai, Jagruti L. AU - Parmar, Mayur P. PY - 2014/10/02 Y2 - 2024/03/28 TI - Application of Box-Behnken design for optimization of formulation parameters for nanostructured lipid carriers of candesartan cilexetil JF - Asian Journal of Pharmaceutics (AJP) JA - AJP VL - 8 IS - 2 SE - Articles DO - 10.22377/ajp.v8i2.343 UR - https://asiapharmaceutics.info/index.php/ajp/article/view/343 SP - AB - This study deals with development and optimization of nanostructured lipid carriers (NLCs) of candesartan cilexetil (CC)<br />for improving its oral bioavailability. From solubility and lipid‑water partition studies of CC in various lipids, glyceryl<br />monostearate (GMS) and glyceryl monocaprylate were selected as solid lipid and liquid lipid, respectively. NLCs were<br />formulated by hot melt‑emulsification‑ultrasonication method. A three‑factor, three‑level Box–Behnken design was used to<br />optimize the independent variables, lipid: drug ratio (X1), solid lipid: liquid lipid ratio (X2) and surfactant concentration (X3).<br />Different batches were prepared and evaluated for responses, particle size (Y1), zeta potential (Y2) and % entrapment<br />efficiency (Y3). Response surface plots and perturbation plots were constructed to study the effect of factors on responses.<br />The optimized formulation containing X1 - 22.47:1, X2 - 7.23:1 and X3 - 1.97% was prepared and evaluated. Observed<br />values for Y1, Y2, and Y3 were found to be closer to the predicted values thus validating the optimization method. Differential<br />scanning calorimetry thermograms of pure drug, GMS and lyophilized drug loaded NLCs indicated complete miscibility<br />of drug into lipids. The release of CC from the NLCs conducted in artificial gastric fluid (pH 1.2) was much higher than in<br />phosphate buffer solution (pH 6.8). The formulated NLCs were found to be more stable at refrigerated condition (5°C ± 3°C)<br />as compared with room temperature (25°C ± 2°C/60% RH% ± 5% RH). The use of design approach helped to identify<br />critical formulation parameters in CC loaded NLCs preparation.<br />Key words: Candesartan, hypertension, nanostructured lipid carriers, oral bioavailability partition study ER -