Salbutamol sulphate is a directly acting sympathomimetic agent with selective action onrnÃŸ2-receptors. It is used as bronchodilator in the management of disorders involvingrnreversible airways obstruction and in chronic obstruction pulmonary diseases. Oralrnsalbutamol sulphate has site-specific absorption in the stomach and upper part of thernsmall intestine. Its bioavailability is about 40% due to extensive hepatic first passrnmetabolism, sulphonation in intestinal fluid, degradation in colon and narrow absorptionrnwindow. The aim of this study was to formulate and optimize a sustained release floatingrntablet of salbutamol sulphate using xanthan gum (XG) and hydroxypropylrnmethylcellulose (HPMC) as release retarding agents and sodiumbicarbonate (NaHCO3)rnas floating aid in order to improve bioavailability, reduce dosing frequency, and increasernpatient compliance.rnThe sustained release floating tablets of salbutamol sulphate was prepared by wetrngranulation technique using XG and HPMC as release retarding polymers. The effects ofrnformulation variables: percentage of polymer (XG, HPMC, or XG/HPMC) andrnpercentage of sodium bicarbonate on response variables: floating lag time, floatingrnduration, cumulative release within 1 hr, and release rate were investigated. Preliminaryrnstudies revealed that the percentage of sodium bicarbonate, percentage of polymer (XG,rnHPMC, or XG/HPMC) significantly affected the floating lag time, cumulative releasernwithin 1 hr and release rate (P < 0.05), but not floating duration. Among the polymersrnused, the one with 1:3 (XG:HPMC) ratio was selected for further optimization purposerndue to that it contains relatively high amount of HPMC, which has low hydration powerrnthan XG, that can release enough amount of drug in the first 1 hr which can be used asrnbolus dose for rapid relief of asthma. The effect of formulation variables on floating lagrntime was significant, but all formulations floated below 10 seconds and not consideredrnduring optimization. The effects of percentage of NaHCO3 and percentage of XG/HPMCrn(1:3) were studied and optimized for maximum desired output of drug release rate andrncumulative release within 1 hr using central composite design statistical approach.rnDesign-Expert 8.0.7.1 software was employed to carry out the experimental design,rnstatistical analysis, and numerical and graphical optimization.rnivrnLinear and quadratic models were developed as best fit models for release rate andrncumulative release at 1 hr, respectively. The analysis of variance (ANOVA) of thernmodels showed that the linear effects of both parameters were significant for the linearrnmodel of release rate; and all the linear, interaction and quadratic effects were significantrnfor the quadratic model of cumulative release at 1 hr. The effect of percentage ofrnXG/HPMC was more pronounced than the effect of percentage of NaHCO3 on bothrnmodels. Finally, simultaneous optimization of cumulative release at 1 hr and release raternwas performed and the most desirable representative optimal point was obtained to havernrelease rate of 28.49 hr-1/2 and cumulative release at 1 hr of 24% at corresponding levelsrnof 24.79% of XG/HPMC and 5% of NaHCO3 with desirability of 0.756. The validity ofrnthis optimal point was confirmed by the low magnitude of percent prediction error.rnEvaluation of the optimized formulation showed successful formulation of the floatingrntablets with excellent granule and tablet property. Comparison of the release profiles ofrnthree different batches of the optimized formulation by dissolution efficiency revealedrnthat there was no statistically significant difference (p > 0.05) in release profiles of thernformulations. In addition, drug release kinetics and drug release mechanism studiesrnindicated that the optimized formulation followed Higuchi square root kinetic model withrnnon Fickian diffusion release mechanism. In conclusion, this study has come up with anrnoptimum formulation for the development of floating tablet of salbutamol sulphate thatrncould remain buoyant and release the drug over a period of 12 hr in a sustained manner inrnvitro.rnKeywords: GRDFs; Floating tablet; Salbutamol sulphate; Xanthan gum; HPMC;rnOptimization