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

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.

Clonidine complexation with hydroxypropyl-beta-cyclodextrin: From physico-chemical characterization to in vivo adjuvant effect in local anesthesia.

Clonidine (CND), an alpha-2-adrenergic agonist, is used as an adjuvant with local anesthetics. In this work, we describe the preparation and characterization of an inclusion complex of clonidine in hydroxypropyl-beta-cyclodextrin (HP-ß-CD), as revealed by experimental (UV-vis absorption, SEM, X-ray diffraction, DOSY- and ROESY-NMR) and theoretical (molecular dynamics) approaches. CND was found to bind to HP-ß-CD (Ka=20M(-1)) in 1:1 stoichiometry. X-ray diffractograms and SEM images provided evidence of inclusion complex formation, which was associated with changes in the diffraction patterns of the pure compounds. NMR experiments revealed changes in the chemical shift of H3HP-ß-CD hydrogens (Δ=0.026ppm) that were compatible with the insertion of CND in the hydrophobic cavity of the cyclodextrin. Molecular dynamics simulation with the three CND species that exist at pH 7.4 revealed the formation of intermolecular hydrogen bonds, especially for the neutral imino form of CND, which favored its insertion in the HP-ß-CD cavity. In vitro assays revealed that complexation retarded drug diffusion without changing the intrinsic toxicity of clonidine, while in vivo tests in rats showed enhanced sensory blockade after the administration of 0.15% CND, with the effect decreasing in the order: CND:HP-ß-CD+bupivacaine>CND+bupivacaine>bupivacaine>CND:HP-ß-CD>clonidine. The findings demonstrated the suitability of the complex for use as a drug delivery system for clinical use in antinociceptive procedures, in association with local anesthetics.

Clonidina versus fentanilo en anestesia epidural en cesáreas: ventajas e inconvenientes / Clonidina versus fentanilo in epidural in Caesarean: advantages and disadvantages

La búsqueda continua de fármacos más seguros y eficaces para la realización de operación cesárea, con efectos adversos mínimos tanto para la madre como para el niño, mejorando la calidad anestésica, ha llevado a investigar el comportamiento de clonidina como adyuvante del bloqueo peridural con bupivacaina al 0.5 por ciento comparada con fentanilo. Explorar la posible ocurrencia de efectos adversos provocados por la administración epidural de clonidina en mujeres sometidas a operación cesárea y compararlos con los producidos por fentanilo. El bloqueo peridural se realizó a un grupo de 100 embarazadas con bupivacaina al 0.5 por ciento sin epinefrina,1 ml por metámera a bloquear (aprox. 18ml) a un grupo de 50 pacientes con el agregado de 100 ug de fentanilo y al otro restante 150 ug de clonidina, al que se tuvo presente tratar anticipadamente la hipotensión leve esperada (inferior al 10 por ciento de la toma basal) con medidas de soporte tradicional y efedrina; y de esa manera poder estudiar y comparar si la posibilidad de anticiparse a la producción o no de hipotensión es efectiva para la atenuación y aparición de ésta complicación y de otras. cesáreas electivas y de urgencias ASA 1y 2, excluidas emergencias y las pacientes que no aceptaron expresamente el consentimiento informado, ingresar en el estudio. Se monitorizaron signos vitales maternos, TA sistólica, diastólica, cardioscopía, pulsioximetría, latidos cardíacos fetales y escore de Apgar. La hemodinamia se mantuvo estable en los dos grupos, aunque la hipotensión fue la reacción adversa de mayor incidencia en el grupo de clonidina, dentro y coincidente con el tiempo de latencia e instalación del bloqueo (17 min. ± 2), respondiendo efectivamente al tratamiento predeterminado. La media del tiempo quirúrgico fue de 57 ± 3.0 minutos con un nivel máximo sensitivo en dermatoma T5 y nivel motor que varió entre 33 por ciento y el 66 por ciento.