Purpose:
To develop and
characterize an oral extended-release matrix tablet of
metformin hydrochloride using a combination of a
hydrophobic carrier and a hydrophilic polymer, and two
types of formulation techniques.
Methods:
Various metformin
hydrochloride formulations containing a hydrophobic
carrier (stearic acid) and a hydrophilic polymer
(polyethylene oxide) were prepared using a 32
factorial design. Two types of formulation techniques –
melt granulation and direct compression – were
evaluated. The influence of the carrier, polymer and
preparation method on metformin release from the
formulations in vitro as well as other physicochemical
properties were studied. The release data were subjected
to various release kinetic models and also compared with
those of a commercial brand.
Results:
The physicochemical
characteristics of all the granules and tablets were
generally satisfactory. Optimization results
indicate that the release rate of metformin HCl was
directly proportional to the levels of stearic acid (SA)
and polyethylene oxide (PEO) in the tablet formulations.
Release rate was also dependent on the method of
granulation used. Kinetic analysis showed that the
formulation containing 30 %w/w of polymer exhibited
release similar to that of the commercial brand with a
similarity factor (f2) of 81.1. Melt granulation was
more effective in extending drug release than direct
compression. Release mechanism followed most closely the
Korsemeyer-Peppas model with a correlation coefficient
(r2) and 0.991.
Conclusion:
The use of a hydrophobic carrier along with a
hydrophilic polymer effectively controls the initial
rapid release of a highly water soluble drug such as
metformin HCl. Hot melt granulation method was
especially more effective in achieving this than the
direct compression method.
Keywords:
Metformin
hydrochloride, Matrix tablets, Polyethylene oxide,
Stearic acid, Hot melt granulation, In vitro release.
