Purpose:
To
prepare oral sustained release matrix tablets of a
highly water soluble drug, tramadol hydrochloride, and
to evaluate the effect of concentration of the
hydrophobic polymer content and
method of preparation on drug release.
Methods:
The tablets were a mixture of both tramadol
hydrochloride and glyceryl palmitostearate (GP) prepared
by melt granulation (MG1, MG2, MG3 and MG4 in ratios
1:1, 1:2, 1:3 and 1:4, respectively) or by direct
compression (DC, 1:2 ratio). The hardness of the tablets
was measured. Drug/GP interaction was determined by FT-IR
spectroscopy while drug release from the matrix tablets
was studied using USP ІІ dissolution apparatus. The
release data were subjected to different models in order
to evaluate their release kinetics and mechanisms.
Results:
The hardness of the tablets was in the range of 5.30 ±
0.36 - 6.50 ± 0.10 kg/cm2. FT-IR spectra
showed that there was no clear interaction between the
drug and the glyceride. Of the formulations (MG1 to MG4)
prepared by melt granulation, MG4 showed the most
suitable sustained release, 58.4 ± 1.1 % in 12 h (p <
0.05). Drug release (98.2 ± 0.2 % in 8 h) was highest
for DC which was prepared by direct compression. Also,
drug release mechanism for the formulations was by
Fickian diffusion.
Conclusion:
Glyceryl palmitostearate is a suitable matrix-forming
agent to sustain the release of a water-soluble drug
such as tramadol hydrochloride. Melt granulation was a
better technique for formulating the product than direct
compression.
Keywords:
Tramadol hydrochloride; Glyceryl
palmitostearate; Melt granulation; Direct compression;
Sustained release.
