Abstract
Purpose: A study was made of the
effects of some bases and adjuvants on the physical and
release properties of metronidazole suppositories with a
view to providing more information for the optimization
of the rectal formulation of metronidazole.
Method: Suppositories (1g) containing
200mg of metronidazole each were prepared in witepsol
(H15 and E75) and polyethylene glycol (PEG 2850 and
4650) bases, using different concentrations of Tween 80,
sodium salicylate and methylcellulose as adjuvants. The
setting time, solidification point and melting range of
the suppositories were determined, along with their
crushing strength, disintegration time and the time for
80% of metronidazole to be released from the
suppositories (t80).
Results: The ranking of setting time
for the suppositories was witepsol H15 > PEG 2850 >
witepsol E75 > PEG 4650, while the ranking of
solidification point, melting range, crushing strength,
disintegration time and the time for 80% of
metronidazole to be released from the suppositories (t80)
was the reverse of that for setting time. Optimal
concentrations of Tween 80 and sodium salicylate were
observed for the suppository formulations. Using
Kitazawa plots, all formulations showed two dissolution
rate constants, k1 and k2
intersecting at time t1, with formulations
containing 5 to 20 % w/w of
methylcellulose exhibiting a third dissolution rate
constant, k3 intersecting with k2
at time t2.
Conclusion: The physical and release
properties of metronidazole suppositories are influenced
considerably by the bases and adjuvants employed. Tween
80 and sodium salicylate can probably be used to
formulate only immediate-release suppositories while
methylcellulose can be useful for sustained-release
metronidazole suppositories. Some insight into these
inferences can be obtained from parameters derived from
Kitazawa plots.
Keywords:
metronidazole, suppository bases, adjuvants, physical
and release properties, Kitazawa plots.
