Box-Behnken Design for Optimization of Formulation Variables of Tramadol HCl Sustained Release Matrix Tablet

Author(s)

Gandhi, C.K., Mehta, T.J., Patel, M.R., Patel, K.R., Patel, N.M.

Author's Affiliation

Abstract

The objective of this work was to develop sustained release tablets (Once in a day) of highly water soluble Tramadol HCl using hydrophilic polymers (HPMC K100M, HPMC K15M, HPMC K 4M) as cost effective, non toxic easily available and suitable hydrophilic matrix system. Sustained release tablet of Tramadol HCl (dose 200mg) were produced by wet granulation method by PVP K30 5% solution. After the evaluation of physical characteristics of granules & tablets, The dissolution test was performed in 0.1 N HCl for 2 hr and remaining 22 hr performed in 6.8 pH buffer solution. We concluded that T1-T15 batches of Box-behnken design passed the pre-compressional and post-compressional parameters and increasing the polymer concentration, decreasing the drug release. Higher viscosity grade HPMC K100M is more drug retarding agent as compare to HPMC K15M & HPMC K4M.  In combination of HPMC K4M, HPMC K15M & HPMC K100M, T7 batch having drug releasing up to 24 hrs as compare to others. Kinetics treatment of the box-behken design batches, concluded that zero order R² value is near to 0.999 as compared to the first order R² value. So, all batches follow the Zero order release mechanism. From the korsmeyer-peppas model, concluded that drug release mechanism is diffusion with dissolution or anomalous diffusion (Non-fickian). From the statastical analysis full model and reduced model was analyzed and got the significant effect of X₃ polymer as compared to X₁ & X₂. X₃ having more negative value than the X₁ & X₂ so concluded that the X₃ polymer is effective to retardation of the drug release. T1-T15 batches are compared with marketed product (Tramazac OD tab.). T7 batch had more 73.58 similarity factor (f₂) when Marketed formulation taken as a reference. So T7 batch is optimized batch. The optimized batch is passed the accelerated stability studies, No significant change in the dissolution profile.

Keywords

Box-Behnken Design, Hydroxypropylmethylcellulose, PVP K-30, Sustained Release, Tramadol HCl, Wet Granulation

Cite This Article

Gandhi, C.K., Mehta, T.J., Patel, M.R., Patel, K.R., Patel, N.M. (2012). Box-Behnken Design for Optimization of Formulation Variables of Tramadol HCl Sustained Release Matrix Tablet, International Journal for Pharmaceutical Research Scholars (IJPRS), 1(2), 99-114.