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Purpose : To develop a zero-order sustained release floating formulation of captopril, and optimize its drug release for enhanced oral bioavailability. Methods : A relatively new approach, 3 2 full factorial design, was used to formulate floating captopril matrix tablets and to systematically optimize its drug release using varying levels of xanthan gum and hydroxypropyl methylcellulose (HPMC) K100M polymers. Calcium carbonate was used as gasgenerating agent. After setting the levels by preliminary trials, nine tablet formulations (F1 - F9) were prepared by wet granulation method using Design Expert Software® - suggested combinations of polymers. The concentrations of HPMC K100M (X 1 ) and xanthan gum (X 2 ) were chosen as control variables. Conversely, the response variables selected were timed to release 50 % of the drug (t 50% ) at 6 h (Q 6 ) and 12 h (Q 12 ). Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) were used to assess compatibility between the drug and the excipients. The validity of the developed mathematical equations was assessed by designing three extra check-points. Results : The response surface plots drawn demonstrated the suitability of the hydrophilic matrixforming agents for formulating controlled release floating tablets of captopril. FTIR and DSC spectra showed no noticeable incompatibility between drug and polymers in both physical mixtures and in formulations. Floating time lag remained 12 h. Considerable agreement was observed between predicted and actual release parameters. Fitting the data into different kinetic models showed that non-Fickian behavior for diffusion exponent (n) differed from 0.588 and 0.811. Conclusion : Optimum formulation (F4) showed satisfactory release profile. Moreover, the study successfully demonstrated influence of polymer blends in controlling release variables. Keywords : Captopril, Xanthan gum, Hydroxy propyl methyl cellulose , Factorial design, Bioavailability

Formulation Optimization and <i>In-vitro</i> Evaluation of Oral Floating Captopril Matrix Tablets using Factorial Design