Purpose:
To develop a floating multiparticulate unit system for
metoprolol tartarate, using a porous carrier, with an
outcome for delayed gastric emptying.
Methods:
Dried microparticles of metoprolol tartarate were
prepared by solvent evaporation using Eudragit®
RS-PO, polypropylene foam powder, and dichloromethane as
release-rate modifying polymer, floating aid and solvent
respectively. The surface topography of the particles
was assessed by SEM while the physical state of the drug
within the developed system was characterised by DSC and
XRD. Drug release was investigated by in vitro
dissolution test. Tc99m sulfur colloid radio-labelled
microparticle formulation was administered to fasting
rabbits and their transit behavior was monitored using
gamma scintigraphy. The anterior and posterior images
recorded were computed to determine the geometric mean
counts, enabling quantitative estimation of gastric
emptying rate.
Results:
Dried free-flowing, white coloured microparticles were
obtained. They were highly porous and also irregular in
shape. The drug in the microparticles was partly
amorphous, showing a decrease in crystallinity. In vitro
drug release from the particles followed a biphasic
pattern with zero-order kinetics. The microparticulate
system exhibited good floating ability with t1/2
of 300 min over the duration of the in vivo study (6 h).
Conclusion:
The developed microparticles showed suitable release
properties, were free-flowing and exhibited good
floating ability in rabbit stomach. Therefore, the
formulation is capable of being further processed into
tablet and/or capsule dosage forms for oral
administration as a gastro-retentive controlled delivery
system.
Keywords:
Metprolol tartarate, Gastro-retention, Eudragit polymer,
Polypropylene foam powder, Gamma scintigraphy,
Microparticulate system, Zero order release.
