Optimization of Aceclofenac Solid Dispersion Using Box-Behnken Design: in-vitro and in-vivo Evaluation

Title:Optimization of Aceclofenac Solid Dispersion Using Box-Behnken Design: in-vitro and in-vivo Evaluation

VOLUME: 11 ISSUE: 3

Author(s):Furqan A. Maulvi, Vaishali T. Thakkar, Tejal G. Soni and Tejal R. Gandhi

Affiliation:Maliba Pharmacy College, Uka Tarsadia University, Bardoli – Mahuva Road, Tarsadi, Dist. Surat 394 350, Gujarat, India.

Keywords:Aceclofenac, Analgesic, Anti-inflammatory, Avicel 200, Box-Behnken Design, HPMC E-5.

Abstract:The study investigates the combined influence of three independent variables in preparation of aceclofenac ternary solid dispersion (SD) by kneading method. A 3-factor, 3-level Box-Behnken design was used. Independent variables selected were microcrystalline cellulose (Avicel 200 = X₁), hydroxypropyl methylcellulose-5 cps (HPMC E-5 = X₂), and ratio of drug to polymer mixture (X₃). Fifteen batches were prepared and evaluated for angle of repose and percentage drug release at 5 minutes (Q₅). The transformed values of variables were subjected to multiple regression analysis to establish a second-order polynomial equation. Contour plots were constructed to evaluate the effects of X₁, X₂ and X₃ on Q₅ and angle of repose. Model was validated for accurate prediction of Q₅ and angle of repose (AR) by performing checkpoint analysis. The computer optimization process and contour plots predict the levels of independent variables as X₁= +0.5, X₂ = -1 and X₃ = +0.35 for maximized response of Q₅ with better flow property. The stability study during 6 months confirms that aceclofenac exhibits high stability in solid dispersion. In vivo studies indicate that optimized ternary solid dispersion provides rapid pharmacological responses in mice and rats compared to marketed formulation.