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

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.

Effect of Tizanidine on Spasticity in Pediatric Patients with Cerebral Palsy: A Systematic Review

“…One potential explanation for its limited use in the pediatric population is that tizanidine is only commercially available in tablet form. A liquid formulation of the drug, which would be more suitable for children, is currently under development and investigation [20,21].…”

Review : Evaluasi Stabilitas dan Inkompatibilitas Sediaan Oral Liquid

“…Stabilitas mikrobiologi menampilkan waktu simpan dari sediaan farmasi selama periode penyimpanan untuk mencegah efek terjadinya kontaminasi mikroba (39). Ketidakstabilan mikrobial pada sediaan farmasi adalah parameter kritis dalam mengevaluasi penampilan dan kualitas produk karena mikroba juga dapat mempengaruhi sifar fisikokimia produk yang akhutnya dapat menurunkan shelf life (40).…”

Tizanidine Nano emulsion: Formulation and in-vitro Characterization

“…The rest of the region on the phase diagrams represent the turbid and conventional emulsions(33) (34). The pseudo-ternary phase diagram plot for different S mix ratio (1:1, 1:2 and 2:1) were shown in the figures (5)(6)(7)(8)(9).…”

“…It is a myotonolytic drug that acts as a central alpha-2 adrenoceptor agonist and is used to treat spasticity in patients who have suffered from cerebral or spinal injury. It is an antispastic drug with efficacy that is comparable to that of baclofen and a tolerance profile that is more favorable (5). It half life 2.1-4.2 hours and bioavailability is 34-40 due to first pass metabolism (6).…”