Introduction

Tizanidine hydrochloride is currently used to treat spasticity associated with various CNS disorders and for painful muscle spasms in muscoskeletal conditions. Tizanidine is a centrally acting agent with a pharmacodynamic profde different from that of myotonolytic drugs currently in use such as diazepam, baclofen, and dantrolene. As an imidazoline derivative, tizanidine has structural similarities with clonidine. Clonidine is known to produce a variety of central nervous system and psychopharmacological actions. Recently, Bennett and Lal reported on the discriminative stimulus properties of clonidine in rats. It was the purpose of this work to evaluate the discriminative stimulus effects of tizanidine in this species and to compare these effects with those of clonidine, pentobarbital, diazepam, fentanyl, morphine, and cocaine.

Tizanidine hydrochloride has been shown to act as an α2-adrenergic agonist. Its mechanism of action is currently under investigation and has not been fully clarified, but it is believed that the pharmacodynamic effects of tizanidine are linked to its α2- adrenergic agonist properties; its imidazolidine receptor binding may also play a role.

Uses

Tizanidine hydrochloride acts centrally as a muscle relaxant. It is used to treat painful muscle spasms, spasticity associated with multiple sclerosis or spinal cord injury, and muscle spasticity in spinal cord disease. Tizanidine hydrochloride is also helpful as an antispasmodic drug.

A market survey indicated that tablet, capsule and gelatin-coated capsule dosages formed with the strength of 2mg, 4mg and 6mg are given by oral route. Tizanidine hydrochloride belongs to BCS class II drug with low solubility and high permeability.

Bioavailability and metabolized

Oral bioavailability of tizanidine hydrochloride is only 34% to 40%. Approximately 95% of the administered doses are metabolized, and 65% are excreted mainly in the urine. It has a short biological half-life of only 2.5 hours, so it must be administered frequently to patients to maintain the therapeutic effect. The drug had poor bioavailability after oral administration because of the extensive first-pass metabolic effect. Tizanidine hydrochloride is an ideal candidate for transdermal delivery because it does not decompose in the skin; it has a low molecular weight and low water solubility. Incorporating tizanidine hydrochloride in microemulgel is an excellent way to overcome first-pass metabolism and improve therapeutic efficiency and patient compliance by reducing the dosing frequency.

Zanaflex?

Zanaflex? (tizanidine hydrochloride) is a central alpha2-adrenergic agonist. Tizanidine HCl is a white to off-white, fine crystalline powder, which is odorless or has a faint characteristic odor. Tizanidine is slightly soluble in water and methanol; solubility in water decreases as the pH increases. Its chemical name is 5-chloro-4-(2- imidazolin-2-ylamino)-2,1,3-benzothiadiazole monohydrochloride. Tizanidine’s molecular formula is C9H8ClN5S-HCl, and its molecular weight is 290.2.

Zanaflex Capsules? are supplied as 2, 4, and 6 mg capsules for oral administration. Zanaflex Capsules? contain the active ingredient, tizanidine hydrochloride (2.29 mg equivalent to 2 mg tizanidine base, 4.58 mg equivalent to 4 mg tizanidine base, and 6.87 mg equivalent to 6 mg tizanidine base), and the inactive ingredients, hypromellose, silicon dioxide, sugar spheres, titanium dioxide, gelatin, and colorants. Zanaflex? tablets are supplied as 4 mg tablets for oral administration. Zanaflex? tablets contain the active ingredient, tizanidine hydrochloride (4.58 mg equivalent to 4 mg tizanidine base), and the inactive ingredients, colloidal silicon dioxide, stearic acid, microcrystalline cellulose and anhydrous lactose.

References

[1] Ph.D., Gary T. Shearman. “Discriminative stimulus effects of tizanidine hydrochloride: Studies with rats trained to discriminate either tizanidine, clonidine, diazepam, fentanyl, or cocaine.” Drug Development Research 10 1 (1987): 27–35.

[2] Sándor L Bek?. “Tizanidine and tizanidine hydrochloride: on the correct tautomeric form of tizanidine.” Acta crystallographica. Section C, Crystal structure communications 68 Pt 1 (2012): o28-32.

[3] Swati Jagdale, Anuruddha Chabukswar, Sujata Brahmane. “Optimization of Microemulgel for Tizanidine Hydrochloride.” Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry 19 2 (2020): 158–179.