Evaluation of physicochemical and microbiological stability of liquid preparation from tizanidine hydrochloride tablets - a Hospital concern

Caren Gobetti,Cássia Virginia Garcia,Ana Lucia Peixoto De Freitas,Andreas Sebastian Loureiro Mendez,Márcio Vinícius Ayres,Andressa Da Silva Bitencourt

doi:10.1590/s2175-97902020000418896

Abstract

Tizanidine hydrochloride is a centrally acting skeletal muscle relaxant, used in the management of spasticity. This drug is commercially available only as tablets, which highlights the need to develop oral liquid formulations. In the hospital environment, this aspect is circumvented by the preparation of suspensions, to allow administration to children and adults with impaired swallowing, but there are no data regarding their stability. The purpose of this study was to evaluate the physicochemical andmicrobiological stability of liquid dosage forms prepared in the hospital environment from tizanidine hydrochloride tablets, applying high performance liquid chromatography (HPLC) and microbiological analysis. A simple and stability-indicating HPLC method was developed and validated for specificity, linearity, limits of detection and quantification, precision, accuracy and robustness. The liquid formulations were placed in amber PET and glass bottles, which were stored under three different conditions: at room temperature, under refrigeration and at 40 oC. The liquid formulations were analyzed and demonstrated chemical stability for 56 days, allowing their use for long periods. However, the determination of microbiological stability showed that these formulations are prone to microbial contamination, which has dramatically reduced its stability to 7 days, in both bottles and at all evaluated temperatures

Highlights

Tizanidine hydrochloride 5-chloro-4-(2-imidazolin2-yl-amino)-2,1,3-benzothiadiazole hydrochloride is a centrally acting skeletal muscle relaxant
A study demonstrated that tizanidine hydrochloride is an effective and safe drug to decrease spasticity in children with cerebral palsy, and concluded on the basis of experimental findings that it could be considered as a useful anti-spastic drug for the treatment of spastic cerebral palsy in childhood
There is an article involving the use of a Cyano column for the same drug (Qi, Wang, Wang, 2002), our experiments did not detect tizanidine hydrochloride with its use

Summary

Introduction

Tizanidine hydrochloride 5-chloro-4-(2-imidazolin2-yl-amino)-2,1,3-benzothiadiazole hydrochloride is a centrally acting skeletal muscle relaxant. It is a central alpha-2 adrenoceptor agonist and myotonolytic agent used to treat spasticity in patients with cerebral or spinal injury. It is an antispastic agent with similar efficacy to that of baclofen and a more favorable tolerability profile (Qi, Wang, Wang, 2002; Sweetman, 2011). Few, limited studies have been conducted on the effect of tizanidine hydrocloride in children. Despite these limited evaluations, many neurologists recommend its use to treat spasticity

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