Abstract:
Preparation of multiple unit floating pulsatile beads of Carvedilol by simple
ionotropic gelation method intended for chronotherapy of hypertension. Pectin and
sodium alginate were used as matrix forming polymer and NaHCO3 was used as
floating agent. Simple acid- base reaction was formed in the generation of the CO2
gas for Floating. 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 CaCl2 on the dependent variables as % entrapment efficiency,
floating lag time and % drug release in 0.1N HCl. Drug loaded multiparticulates were
evaluated for various parameters like particle size measurement, flow properties, %
drug entrapment, floating study, and dissolution study. Based on minimum drug
release in 0.1 N HCl and after 6 h lag time period and maximum release in 6.8 pH
phosphate buffer by burst release within 45 minutes, formulation containing 300 mg
sodium alginate, 225 mg sodium bicarbonate and 4 % of CaCl2 was optimized and
tested for drug release pattern, floating lag time and entrapment efficiency. 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 validity of the generated mathematical model for each response was checked by preparing three extra-design check point batches and the comparable results of
predicted and actual values validated the design. Stability (at 400/75% relative
humidity for 1 month) studies on the formulation indicated that there were no
significant changes in drug content, floating lag time, entrapment efficiency and drug
release in 0.1 N HCl. Thus, the floating beads were successfully formulated for
chronotherapy of hypertension giving site- and time specific release of drug.