Development and statistical optimization of carvedilol floating beads for chronotherapeutic drug delivery

Abstract

Background and Aims: The aim of the present research work was to develop and optimize statistically carvedilol floating beads for chronotherapeutic drug delivery. Methods: Multiple unit floating pulsatile beads of carvedilol were prepared by simple ionotropic gelation method intended for chronotherapy of hypertension. Pectin and sodium alginates were used as matrix forming, polymer and sodium bicarbonate was used as floating agent. A 23 full factorial design was applied to investigate the combined effect of three independent formulation variables namely amount of sodium alginate, sodium bicarbonate and calcium chloride on the dependent variables as % entrapment efficiency, floating lag time and drug release percentage. Results: The formulation was optimized and tested based on its drug release pattern which presented minimum drug release in 0.1 N HCl and after 6 h lag time period and showed maximum drug release in 6.8 pH phosphate buffer by burst release within 45 mins. Surface response plots were presented graphically to represent the effect of independent variables on floating lag time, entrapment efficiency and drug release in 0.1 N HCl. The generated mathematical model for each response was validated and checked by formulating three extra-design checkpoint batches. There were no significant changes in drug content, floating lag time, entrapment efficiency and drug release of the formulation following its stability studies at 40 0 C and 75% relative humidity. Conclusion: It was concluded that the floating beads were successfully formulated for chronotherapy of hypertension giving site- and time specific release of drug.

Keywords

• Floating beads
• drug release
• chronotherapy
• ionotropic gelation
• hypertension

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