Application of Box-Behnken Design for the Development of Isosorbide Mononitrate Sustained Release Matrix Tablets

作者：Adnan Sherjeel; Shehzadi Kanwal; Farooq Muhammad^*; Ranjha Nazar M; Hanif Muhammad; Masood Zeeshan; Zaman Muhammad

来源：Latin American Journal of Pharmacy, 2016, 35(5): 1018-1025.

• Box- Behnken design
• hydrophilic and hydrophobic polymer
• isosorbide mononitrate
• sustained release matrix

In the present study, sustained release matrix formulations of isosorbide mononitrate (ISMN) were formulated using hydrophilic and hydrophobic polymers by using Box-Behnken design. Thirteen batches of matrix tablets of ISMN were produced by wet granulation. The flow properties of granules and physical parameters of compressed tablets were evaluated. The granules produced good flow properties as evidenced by their bulk density, tapped density, Hausner's ratio, angle of repose, and Carr's index. All physical characteristics of formulated matrix including weight variation, hardness, thickness, and friability fell within acceptable limits. In vitro release study of the drug was performed in phosphate buffer of pH 6.8 over 12 h with reference ISMN tablet (Monis XR). Different kinetic models were applied to the drug release data, in order to evaluate release mechanism and kinetics. The drug release data of FI, FV, FVI, FXI, FXII fitted in to Higuchi model (R-2 = 0.897-0.934). Drug release was found to be a complex mixture of diffusion, swelling, and erosion. Remaining formulation exhibiting zero order kinetics indicating that drug release is independent of residual concentration of drug. From the results obtained, solid matrix F1revealed comparable release profile with reference (Monis XR) sustained release.

• 出版日期2016