RESUMEN
Ondansetron HCl is a (5-HT3) serotonin receptor antagonist, used as anti-emetic drug in combination with anticancer agents. Conventional dosage forms have poor bioavailability and patient compliance. These problems can be reduced by the use of nasal niosomal thermo-reversible in situ gelling system. Niosomes were formulated using various surfactants (Span 60, Span 80, Tween 20, and Tween 80) in different ratios using the thin-film hydration technique. Niosomes were evaluated for particle size, zeta potential, transmission electron microscopy (TEM) imaging, drug entrapment efficiency, and in vitro drug release. Niosomes prepared using Span 60 and cholesterol in the ratio 1:1 (F5) showed higher entrapment efficiency (76.13 ± 1.2%) and in vitro drug release (91.76%) after 12 h was optimized. The optimized niosomes were developed into thermo-reversible in situ gel, composed of Poloxamer 407 and sodium carboxymethyl cellulose, prepared by cold method technique. Compatibility study (FTIR, DSC) was made for drugs and excipients that showed no significant interaction. The gel formulation G5 showed the most suitable gelation temperature (31 °C), viscosity (1250 mpoise), bioadhesion force (5860 ± 28 dyne/cm2), and in vitro drug release (70.6%) after 12 h. Comparative in vivo pharmacokinetic study on rabbits showed a sustained release and higher relative bioavailability of the prepared nasal in situ gel compared to similar dose of oral tablets (202.4%) which make ondansetron HCl niosomal nasal thermo-sensitive in situ gel a more convenient dosage form for the administration of ondansetron HCl than oral tablets.
Asunto(s)
Composición de Medicamentos/métodos , Sistemas de Liberación de Medicamentos/métodos , Mucosa Nasal/efectos de los fármacos , Ondansetrón/administración & dosificación , Ondansetrón/síntesis química , Administración Intranasal/métodos , Animales , Antieméticos/administración & dosificación , Antieméticos/síntesis química , Antieméticos/metabolismo , Evaluación Preclínica de Medicamentos/métodos , Liberación de Fármacos/efectos de los fármacos , Liberación de Fármacos/fisiología , Liposomas , Masculino , Mucosa Nasal/metabolismo , Ondansetrón/metabolismo , ConejosRESUMEN
The oral control drug delivery is the most acceptable delivery system for patient acceptance, industrial application and economical but still it has several challenges to design a dosage form. The gastro intestinal pHis one of the major limitations for constant drug release due to different pH variations different regions (stomach vs small intestine) throughout the GIT. The aim of the present research work was to develop a pH independent oral control release drug delivery of pH dependent Ondansetron HCl for the treatment of CINV or PONV. The major limitation of the drug was found burst release in SGF pH 1.2 and highly precipitation in intestinal pH (pH 6.8 phosphate buffer). The formulator is challenging to develop constant controlled drug release in entire gastro intestinal tract. The techniques involve the use of pH modulating agents and acidifying agents to achieve pH independent controlled drug release. It was found that incorporation of anionic polymer (Eudragit L100-55) with control release nonionic HPMC matrix shows pH independent drug release in both SGF pH 1.2 and pH 6.8 phosphate buffer. In conclusion it was understood that the release profile of HPMC sellable matrices of Ondansetron HCl with manipulating the micro environmental pH, at variable pH conditions provided a efficient and predictable results.
Asunto(s)
Diseño de Fármacos , Desarrollo de Medicamentos/métodos , Ondansetrón/síntesis química , Ondansetrón/farmacocinética , Preparaciones de Acción Retardada/síntesis química , Preparaciones de Acción Retardada/farmacocinética , Liberación de Fármacos , Concentración de Iones de Hidrógeno , Espectroscopía Infrarroja por Transformada de Fourier/métodos , ComprimidosRESUMEN
Objective: This review was prepared to offer the most complete information about the use of ondansetron in parenteral admixtures with other drugs. Method: The search was done from September 2016 to April 2017 by using electronic databases Stabilis® and Micromedex® solutions, Medline/PubMed and Scholar Google searching publications about ondansetron stability in parenteral infusion when is administered by itself or with other medication. Results: 49 studies are included with a total of 53 drugs. 15 drugs were found compatible administered with ondansetron in a clinical routine concentration range in intravenous administration. Also, four ternary blends were found compatible and another one was incompatible. Otherwise, 38 drugs were found incompatible. Conclusions: Compatibility of ondansetron offers a broad number of options to be used to avoid nausea and vomiting symptoms in patients with other concomitant medication (AU)
Objetivo: Esta revisión ha sido preparada para recopilar toda la información referente a la estabilidad del ondansetrón en mezclas parenterales junto a otros fármacos. Método: La búsqueda fue realizada entre septiembre de 2016 y abril de 2017 empleando bases de datos electrónicas como Stabilis® y Micromedex® solutions, Medline/PubMed y Google Académico buscando publicaciones sobre la estabilidad del ondansetrón para infusión vía parenteral cuando es administrado en monoterapia o en una mezcla con otros fármacos. Resultados: En este trabajo han sido incluidos 49 artículos con un total de 53 fármacos. 15 fármacos han sido descritos como compatibles con ondansetrón en concentraciones habituales en la clínica práctica para administración intravenosa. Además, cuatro mezclas ternarias han sido descritas como compatibles y una como incompatible. Por otro lado, 38 fármacos han sido descritos como incompatibles para su administración con ondansetrón. Conclusiones: La compatibilidad del ondansetrón ofrece un amplio rango de opciones para evitar los síntomas de náuseas y vómitos en pacientes con otra medicación concomitante (AU)