Two viscosity grades of hydroxypropylmethylcellulose (HPMC 4000 and 15,000 cps) and Carbopol 934P were used to prepare captopril floating tablets. In vitro dissolution was carried out in simulated gastric fluid (enzyme free) at 37 degrees C +/- 0.1 degree C using the USP apparatus 2 basket method. Compared to conventional tablets, release of captopril from these floating tablets was apparently prolonged; as a result, a 24-hr controlled-release dosage form for captopril was achieved. Drug release best fit both the Higuchi model and the Korsmeyer and Peppas equation, followed by first-order kinetics. While tablet hardness and stirring rate had no or little effect on the release kinetics, tablets hardness was found to be a determining factor with regard to the buoyancy of the tablets.

No abstract

Hydroxypropyl methylcellulose (HPMC-4000cps, fixed amount), various contents of calcium hydroxide, stearyl alcohol, magnesium stearate, different drug: PVP ratios and altered tablet hardness were used to design floating tablet formulation capable to deliver glibenclamide in a sustained manner. Both full factorial and Box-Wilson designs, in consecutive manner, were used to investigate for the influences of these formulation variables on the developed dosage form performance and drug release.Tablet hardness has revealed an influential effect on tablet onset of floating, and drug release was shown to be more evident in the initial phase (p<0.05). Loading level of calcium hydroxide, stearyl alcohol and tablet swellability all have showed profound enhancing effects on duration of tablet buoyancy and drug release.Glibenclamide release from tablets of the invention was shown to follow the anomalous type (n=0.8212-1.0244). Application of statistical and mathematical modeling has enabled the optimization of the developed tablet formulation to meet selective constraints for floating, hardness and drug release.The optimized buoyant tablet formulation with highest CI revealed hardness of 50 N, immediate onset of floating and floating duration >6 hours. Concerning drug release, the formula showed evidence of 25 and 84% drug release after 1 and 6 hours, respectively, with T50% of 3 hours. Moreover, release kinetics of the drug from the optimized formula was shown to be near the desired zero order type of release (n=0.8897 or 0.0132; r2=0.9993). The in vivo dosage form residence time study in six human subjects demonstrated that the developed tablet formulation retained in the stomach for more than four hours under fasting conditions.Comparative bioavailability study revealed that floating tablets showed 2-2.5 times increase in AUC (p≤ 0.1) indicating the sustained release tendency of the drug from the floating tablet formulation.The three months based stability study indicated that the drug and the dosage form retained their initial physical characters in both accelerated and normal conditions for the test duration as far as blister pack is considered.

Objective: The aim of this study was to explore the individual and joint effects of drug: ethylcellulose ratio, content of tween 80 and chloroform: water volume ratio on particles' size and size distribution of artemether loaded ethyl cellulose nanosuspension formulations, aiming to achieve nanosuspension with desired particles properties, stability and drug release profile.Methods: Mixed levels design was used to generate a series of artemether loaded ethylcellulose nanosuspensions that produced by emulsificationsolvent evaporation technique. Formulations were qualified for particle size and size distribution using dynamic light scattering technique. Best ranked formulation was then evaluated for stability and drug release rate and kinetics.Results: Drug: polymer ratio, content of surfactant and organic: water volume ratio were found to exert considerable influences (p<0.05) on particle size of produced nanosuspensions, either individually or as joint variables. Peak intensity property of nanosuspensions was found to be influenced by drug: polymer ratio (p<0.05) whereas the influences of different variables on the polydisperse index property appear inconsequential (p>0.05). Best ranked (optimal) artemether nanosuspension proved stable and capable to improve and maintain the release of loaded drug over 24 h, at least under the setting conditions of this study. Conclusion:Focusing on both the individual and joint influences of formulation variables assist in achieving nanosuspension with desired particles characteristics, stability and drug release profile.

Objective: To investigate the possible individual and joined influences that binding solution concentration, drying temperature and drying duration might have on the physiochemical attributes of granules and tablets using norfloxacin as a model drug. Methods: According to implemented 23 central composite designs, each of the investigated variables were examined at 5 different levels through different 16 formulation runs. For each formulation, obtained granules were qualified for their bulk density, tap density, Hausner ratio, percent of fine and drug content properties whereas the respective tablets were evaluated for their weight variation, drug content, friability, hardness, disintegration, and drug dissolution attributes. Results: Indicated that concentration of binder solution, as compared to drying temperature and drying duration, measured more profound influences on granules' tap density, Hausner ratio, % fine and drug content either through its individual linear and quadratic effects or through its joint effect with drying durations (p<0.05 at 95% CI for all influences). Whilst tablets' friability appeared to be noticeably influenced by the three investigated variables (P ranged 0.001-0.017 at 95% CI), tablets' hardness and disintegration were found to be considerably affected only by binder solution concentration (p = 0.001 and 0.082 at 95% CI, respectively). Moreover, none of the investigated variables has measured a significant influence on tablets' drug content or drug dissolution properties. Conclusion: The study concluded that quadratic and joint influences of variables on attributes of granule and tablet formulations shouldn't be overlooked and better to be considered in the screening design.