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New generation of amphiphilic vesicles known as aspasomes were investigated as potential carriers for transdermal delivery of tizanidine (TZN). Using full factorial design, an optimal formulation was developed by evaluating the effects of selected variables on the properties of the vesicles with regards to entrapment efficiency, vesicle size and cumulative percentage released. The optimal formula (TZN-AS 6) consisting of 20 mg TZN, 50 mg ascorbyl palmitate (AP), 50 mg cholesterol (CH) and 50 mg Span 60, represented well dispersed spherical vesicles in the nanorange sizes and exhibited excellent stability under different storage conditions. Ex-vivo permeation studies using excised rat skin showed a 4.4-fold increase of the steady state flux in comparison to the unformulated drug (p < 0.05). The pharmacokinetic parameters obtained from the in-vivo study using Wistar rats, showed that the bioavailability of TZN was enhanced significantly (p < 0.05) when compared to the oral market product of TZN, Sirdalud®. Moreover, skin irritancy tests confirmed that the vesicles were non-invasive and safe for the skin. Based on the results obtained, the optimised aspasomes formula represents a promising Nano platform for TZN to be administered transdermally, thus improving the therapeutic efficacy of this important muscle relaxant.

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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

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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.

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Tizanidine hydrochloride is a skeletal muscle relaxant used for the treatment of spasm, a sudden involuntary muscle contraction leading to pain. The presently available oral dosage form has limitations such as high first pass metabolism resulting in low oral bioavailability. The short half-life necessitates its frequent administration to maintain the required plasma concentration. Transdermal delivery of drug avoids its first pass hepatic metabolism and gives controlled release, making it possible for reduction in dosing frequency. Drug delivery through transdermal route is severely limited by the presence of a tough stratum corneum barrier. A penetration enhancement approach is often necessary to achieve desired plasma concentrations. Microneedles are very short and sharp needles which do not cause pain. Thus, in the present investigation, preparation and evaluation of a transdermal delivery system for tizanidine hydrochloride based on microneedles are described.

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Bilosomes were developed in order to investigate their efficacy as nanocarriers for transdermal delivery of Tizanidine HCl (TZN), a skeletal muscle relaxant with low oral bioavailability. Full factorial experimental design consisting of 27 combinations was generated to study the effects of surfactant type, surfactant-to-cholesterol ratio and the amount of bile salt on the entrapment efficiency (EE), the vesicle size (VS) and in vitro dissolution of the TZN-loaded bilosomes. The permeation through the stratum cornea was optimized with the vertical diffusion assembly using excised rat skin. The permeation parameters of the selected bilosomes were compared to the unformulated drug and it was shown that TZN-B24 exhibited the highest enhancement ratio (ER = 8.8).The optimal formula (TZN-B24) consisting of span 60 in a ratio with cholesterol of 1:1 and 20 mg of bile salt was obtained by employing the desirability function of Design-Expert® software. The mathematical model used for the optimization was validated by comparing the predicted values of the EE (82.3%) and the VS (165.8 nm) with the experimental values of EE = 84.42% and of VS = 161.95 nm. TZN-B24 displayed high zeta potential which contributed to its good stability. It was evident from the results of this study that incorporating TZN in bilosomes improved significantly its permeation through the skin barrier and thus bilosomes can offer a potential nanoplatform using the transdermal route to improve the bioavailability of the drug.

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OBJECTIVE: This study was designed to optimize and develop matrix type transdermal drug delivery system (TDDS) containing tizanidine hydrochloride (TZH) using different polymers by solvent evaporation method. SIGNIFICANCE: A strong need exists for the development of transdermal patch having improved bioavailability at the site of action with fewer side effects at off-target organs. METHODS: The patches were physically characterized by texture analysis (color, flexibility, smoothness, transparency, and homogeneity), in vitro dissolution test and FTIR analysis. Furthermore, functional properties essential for TDDS, in vitro percentage of moisture content, percentage of water uptake, in vitro permeation by following different kinetic models, in vivo drug content estimation and skin irritation were determined using rabbit skin. RESULTS: The optimized patches were soft, of uniform texture and thickness as well as pliable in nature. Novel transdermal patch showed ideal characteristics in terms of moisture content and water uptake. FTIR analysis confirmed no interaction between TZH and cellulose acetate phthalate (CAP). The patch showed sustained release of the drug which increased the availability of short acting TZH at the site of action. The patch also showed its biocompatibility to the in vivo model of rabbit skin. CONCLUSIONS: The results demonstrated that topically applied transdermal patch will be a potential medicated sustain release patch for muscle pain which will improve patient compliance.

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