Background: The study was to develop an extended release (ER) encapsulated and compacted pellets of Atenolol\nusing hydrophobic (wax based and polymeric based) and high viscosity grade hydrophilic matrix formers to control\nthe release of this highly water soluble drug by extrusion/spheronization (ES). Atenolol is used for cardiovascular\ndiseases and available as an immediate release (IR) tablet dosage form. The lipids, Carnauba wax (CW), Glyceryl\nmonostearate (GMS) and cellulose based i.e. Hydroxypropyl methylcellulose (HPMC) and Ethyl cellulose (EC) were\nused in preparing Atenolol ER pellets. Thermal sintering and compaction techniques were also applied to control\nthe burst release of Atenolol.\nMethod: For this purpose, thirty-six trial formulations (F1-F36) were designed by Response Surface Methodology\n(RSM), using Design-Expert 10 software, keeping (HPMC K4M, K15 M & K100 M), (EC 7FP, 10FP & 100FP), waxes\n(GMS, & CW), their combinations, sintering temperature and duration, as input variables. Dissolution studies were\nperformed in pH, 1.2, 4.5 and 6.8 dissolution media. Drug release kinetics using different models such as zero order,\nfirst order, Korsmeyer-Peppas, Hixon Crowell, Baker-Lonsdale and Higuchi kinetics were studied with the help of\nDDsolver, an excel based add-in program.\nResults: The formulations F35 and F36 showed compliance with Korsmeyer-Peppas Super case II transport model\n(R2 = 0.975ââ?¬â??0.971) in dissolution medium pH 4.5. No drug excipient interaction observed by FTIR. Stereomicroscopy\nshowed that sintered combination pellets, (F35), were highly spherical (AR = 1.061, and sphericity = 0.943). The\ncross-sectional SEM magnification (at 7000X) of F34 and F35 showed dense cross-linking. The results revealed that\nthe optimized formulations were F35 (sintered pellets) and F36 (compacted pellets) effectively controlling the drug\nrelease for 12 h.\nConclusion: Extended-release encapsulated, and compacted pellets were successfully prepared after the\ncombination of lipids CW (10%) and GMS (20%) with EC (10FP 20% & 100FP 20%). Sintering and compaction, in\naddition, stabilized the system and controlled the initial burst release of the drug. Extended release (ER) Atenolol is\nan effective alternative of IR tablets in controlling hypertension and treating other cardiovascular diseases.
Loading....