NOVEL CHRONOTHERAPEUTIC MULTIPARTICULATE DRUG DELIVERY SYSTEM OF FELODIPINE: AN EFFECTIVE TREATMENT FOR CARDIAC ARRHYTHMIA
Abstract: Arrhythmia follows
chronobiology, thus necessitating development of time-dependent formulation for
its treatment. The aim of the current work was to develop a solubility-enhanced
chronotherapeutic system of felodipine, a widely prescribed anti-arrhythmic.
Systematically optimized hot-melt extrusion process was employed to formulate
solubility-enhanced extrudates. Film-casting method was adopted for the
selection of polymers. Drug released at 5, 15, 30min was taken as response
variables in 32 face-centered cube design. Nearly 10-fold increase was observed
in the solubility of the optimized extrudates in comparison to pure drug.
Physical characterization of the extrudates depicted complete amorphization of
drug. Sequential coating was performed on to the extrudates to enable a
time-dependent release. In-vitro studies clearly demonstrated that 25% of drug
was available rapidly within 10 min of administration. The remaining 75% of
drug was available over a period of 4, 8 and 12h. Stability studies performed
for 6 months at accelerated conditions depicted no significant change in the
physicochemical characteristics of the optimized formulation. In-vivo
pharmacokinetic studies conducted in beagle dogs ratified the results of
in-vitro studies where a sequential time dependent absorption of felodipine was
observed over a period of 12h. Concisely, the studies demonstrated successful
development of solubility-enhanced chronotherapeutic system of felodipine.
Keywords: hot-melt; central
composite design; pharmacokinetics; arrhythmia; extrudates
Author: Sabyasachi Banerjee, K
Ravi Shankar, Y Prasad Rajendra
Journal Code: jpfarmasigg170012
