Development and Stability Control of Pediatric Oral Tizanidine Hydrochloride Formulations for Hospital Use

• Published in: AAPS PharmSciTech Vol. 21; no. 6; p. 210
• Main Authors: Gobetti, Caren, Balsan, Maria Eduarda, Ayres, Márcio Vinícius, de Almeida, Sílvia Helena Oliveira, de Saldanha Simon, Elisa, Wingert, Nathalie Ribeiro, Oppe, Tércio Paschke, Garcia, Cássia Virginia
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 29-07-2020
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Pharmacology/Toxicology; Pharmacy; Research Article; liquid formulations; tizanidine hydrochloride; physicochemical and microbiological stability; Box-Behnken design; pediatric
• ISSN: 1530-9932; 1530-9932
• DOI: 10.1208/s12249-020-01751-8

Tizanidine hydrochloride is a centrally acting skeletal muscle relaxant used in the treatment of spasticity. This drug is sold only as tablets or capsules, which highlights the need to develop oral liquid formulations that allow administration to children and adults with impaired swallowing. This study aim was to develop and improve tizanidine hydrochloride liquid formulations from raw material and to evaluate their stability. A stability-indicating high performance liquid chromatography method was validated for two formulations developed. Fifteen formulations were developed containing syrup and fifteen containing sodium carboxymethyl cellulose as vehicles, to select the two most suitable for stability testing. The formulations were prepared in triplicate and placed in amber polyethylene terephthalate and glass bottles, which were stored under three different conditions: at room temperature (15–30°C), under refrigeration (2–8°C), and at 40°C. The physicochemical and microbiological stability of formulations were evaluated, applying high performance liquid chromatography and microbiological count. The studied formulations at 15–30°C, 2–8°C, and 40°C can be used for a period of 70 days, and all parameters are inside of recommended specifications, enough to allow its use in the context for which it was developed, the application in hospital. The formulations developed in this work have simple components to avoid adverse reactions in vulnerable populations. Results of this study could be applied as a reference for hospital use; once it demonstrated the reliability of storage time interval and proper conditions for use.