Design, Evaluation and Optimization by Central Composite Design of Effervescent Floating Tablets of Norfloxacin Using Natural Polymers

作者：Ashgar Anam^*; Sethi Ayesha; Hanif Muhammad; Sharif Kanwal; Akhtar Naveed; Chowdhary Farzanah; Masuud M Irfan; Awan Malik A B

来源：Latin American Journal of Pharmacy, 2015, 34(3): 496-507.

• central composite design
• gastroretentive effervescent floating tablets
• HPMC K 15
• MCC
• norfloxacin
• Psyllium husk

This study consists of two parts: first, formulation and evaluation of effervescent floating tablets of norfloxacin using natural polymers by the application of Central Composite design (CCRD); second, analyzing the effect of independent variables (HPMC K15, Psyllium husk and MCC) on dependent variables i.e. flow properties (Hausner's ratio, Carr's index, angle of repose) in term of responses by using CCRD. The ranges of variables used in the design were HPMC K15 (10-20%), Psyllium husk (1-4%) and MCC (14-20%). Fifteen formulations were designed by using central composite design, of which 6 formulations with good flow properties were subjected to compression by wet granulation method. Tablets were analyzed for parameters like hardness, friability, weight variation, swelling index, floating lag time, floating duration, bio adhesive studies and drug dissolution studies. Firstly, dissolution studies were conducted by varying polymers HPMC K15 and Psyllium husk concentration. Drug release was very less during 8 h i.e. <40%. Surfactant SDL 1% was then used in order to investigate its effect on drug release and it was found that drug release improved in a manner that it was not abrupt. 1.2 pH 0.1 N HCl and pH 4 buffer media were used for analyzing the maximum drug release in 8 h. As 0.1 N HCl gives much better drug release, up to 32% than 28% during 8 h. So, for selected 6 formulations 0.1 N HCl medium was used for drug release. Among 6 formulations best considered formulation F3 give 96% drug release during 8h and the floating lag time was 19 s. Drug release of selected formulations was further investigated by model dependent (first order, zero order, Higuchi and Krosmeyer equation) and model independent approach (f1 and f2) factor. All formulations follow 1st order of release kinetics and mechanism of drug release was found anomalous i.e. diffusion and swelling as value of "n" falls between 0.5-0.89. FTIR studies indicate compatibility of norfloxacin with polymers HPMC K15 and Psyllium husk. RSM was applied for graphical presentation of effect of independent variables on dependent variables. ANOVA values found between moderately significant to significant for Hausner's ratio (0.0473), for Carr's index (0.0246) and for angle of repose (0.0292).

• 出版日期2015