Purpose: To formulate
sustained-release (SR) matrix tablets of tizanidine
hydrochloride (THC) and to investigate the effect of
matrix polymer type on drug release profile of drug.
Methods: Matrix tablets of THC were
prepared by direct compression method using a
combination of hydroxypropylmethylcellulose (HPMC) and
ethylcellulose (EC) in varying ratios. In all the
formulations, the amount of THC was 6.87 mg (equivalent
to 6 mg base). USP type-I (basket) apparatus was used
for the dissolution study. The dissolution study was
performed in 0.1M HCl for the first 2 h and in phosphate
buffer (pH 6.8) for another 10 h. The dissolution data
were subjected to drug release models to ascertain the
kinetics of drug release. Additionally, in vitro
swelling and buoyancy studies were carried out on the
optimized formulation. The optimized formulation was
compared with a commercial reference product using
similarity factor (ƒ2) test.
Results: F4 formulation, containing
145 g of HPMC only, (with ƒ2 value of 67.38)
was selected as optimized formulation (compared to the
reference commercial product), and it released 97.84 %
of the drug in 12 h. The release data showed best fit to
first-order kinetics (R2 = 0.9963 - 0.9989),
though non-significantly (p > 0.05) different from the
Higuchi model (R2 = 0.9813 - 0.9955) except
for formulation F6. Based on Koppcha model data, drug
release mechanism involved both diffusion and erosion (n
= 0.513 - 0.597) with diffusion being dominant. The
optimized formulation exhibited 162 % swelling at the
end of 11 h, after which no further weight gain
occurred.
Conclusion: Suitable sustained-release
tablets of tizanidine hydrochloride have been
successfully prepared using direct compression Drug
release is sustained by increasing the content of the
matrix polymers used.
Keywords: Tizanidine, HPMC, EC,
Koppcha, Hixson-Crowell, Stokes-Einstein’s equation
