Development and Optimization of Proniosomal Gel Containing Etodolac: In-vitro, Ex-vivo and In-vivo Evaluation / Desarrollo y optimización del gel proniosomal que contiene etodolaco: evaluación in vitro, ex vivo e in vivo

Introducción: Etodolac se usa en el tratamiento del dolor agudo y la inflamación. Tiene baja solubilidad debido a la alta hidrofobia y se informa que tras la administración oral muestra alteraciones gástricas. Esto fomenta el desarrollo de formulación tópica en lugar de oral. Método: En este trabajo utilizamos el método de separación de fase de coacervación para el desarrollo del sistema vesicular cargado con etodolaco mediante el uso de tensioactivos no iónicos, colesterol y lecitina de soja. El diseño central compuesto (rotativo) se utilizó para optimizar las concentraciones de lecitina de soja, surfactante y colesterol. Las formulaciones preparadas se caracterizaron por análisis de tamaño de vesículas, potencial zeta, eficiencia de atrapamiento, permeación in vitro, permeación ex vivo y estudio antiinflamatorio. Resultados: Etodolac quedó atrapado con éxito en todas las formulaciones que tenían una eficiencia en el intervalo de 74,36% a 90,85%, siendo mayor a 4 ° C que a temperatura ambiente. Cuando se hidrata con agua, los niosomas se producen espontaneamente el rango de 54 a 141 (por mm cúbico). Los resultados del estudio de difusión in vitro revelaron que el etodolaco se liberó en un rango de 71,86 a 97,16% durante un período de 24 horas. El tamaño medio de vesícula de la formulación optimizada se encontró en 211,9 nm con un PDI de 0,5. Las respuestas observadas, es decir,% de eficacia de encapsulación y liberación de fármaco, fueron 74,12 y 95,08 respectivamente. El potencial zeta fue de -19,4 mV y reveló la estabilidad de la formulación, que fue confirmada adicionalmente por la ausencia de cambios en el contenido del fármaco y la liberación del fármaco después de los estudios de estabilidad. El% de inhibición en el volumen de la pata fue del 40,52% y del 43,61% para la prueba y el gel proniosómico comercializado. (AU)

Introduction: Etodolac is used in the treatment of acute pain and inflammation. It has low solubility because of high hydrophobicity and it is reported that upon oral administration shows gastric disturbances. This encourages the development of topical vesicular formulation. Method: In this work we used coacervation-phase separation method for the development of etodolac loaded ve-sicular system by using non-ionic surfactants, cholesterol and soya lecithin. Central composite design (rotatble) was used to optimize the concentrations of soy lecithin, surfactant and cholesterol. The prepared formulations were characterized by number of vesicles formed, vesicle size, zeta potential, entrapment efficiency, in-vitro permeation, ex-vivo permeation and anti-inflammatory study. Results: Etodolac was successfully entrapped in all formulations having efficiency in the range of 74.36% to 90.85%, which was more at 4 °C than room temperature. When hydrated with water; niosome in the range of 54 to 141 (per cubic mm) were spontaneously produced. The results of in-vitro diffusion study revealed that etodolac was released in the range of 71.86 to 97.16% over a period of 24 hrs. The average vesicle size of optimized formulation was found 211.9 nm with PDI of 0.5. The observed responses i.e. % encapsulation efficiency and drug release were 74.12 and 95.08 respectively. The zeta potential was -19.4mV revealed the stability of formulation which was further confirmed by no changes in drug content and drug release after stability studies. The % inhibition in paw volume was 40.52% and 43.61% for test and marketed proniosomal gel. (AU)

Formulation development, in vitro and in vivo evaluation of microemulsion-based gel loaded with ketoprofen.

BACKGROUND: Anti-inflammatory agents are widely used to relieve inflammation caused by various factors. AIM: This study was initiated with the intention to deliver low aqueous soluble ketoprofen to enhance its solubility by developing microemulsion system as a template and then incorporating it into gel phase. MATERIALS AND METHODS: Initially ketoprofen was solubilized into microemulsion preparation made up of clove oil, Tween 20 and propylene glycol as oil phase, surfactant and co-surfactant respectively, then it was incorporated into different concentration of gelling phase using gelling agents namely Carbopol 940, Carbopol 934 and hydroxypropyl methyl cellulose K(4)M (HPMC K(4)M). Formulated emulgels were evaluated for their physical appearance, pH, rheological properties, globule size, extrudability, drug content, spreadability, bioadhesion strength, in vitro and ex vivo drug release, skin irritation test and anti-inflammatory activity. RESULTS: Microemulsion had shown globule size 396 nm, pH 6-6.7, viscosity 29.4 cps and zeta potential -12 mV indicating good stability. Formulated emulgels showed good physical appearance, skin acceptable pH 6-6.9, non-Newtonian shear thinning system, drug content 99.28 ± 0.16%, bioadhesion strength 48.4 gram force, globule size 473 nm, spreadability 22.96 gm.cm/s, good extrudability, in vitro release, ex vivo release did not showed any irritation reaction and possess a good anti-inflammatory activity. CONCLUSIONS: Selected batch showed enhanced drug release (92.42 ± 4.66%) as compared to marketed gel (65.94 ± 3.30). Similarly ex vivo release of formulation showed 72.22% release through mice skin compared with marketed gel. Formulations followed Korsmeyer-Peppas diffusion kinetic model. It was observed from the results that the formulated emulgel can provide promising delivery of ketoprofen.

Characterization of gliclazide-polyethylene glycol solid dispersion and its effect on dissolution / Caracterização de gliclazida polietileno-glicol dispersão sólida eo seu efeito sobre a dissolução

The present study was initiated with the objective of studying the in vitro dissolution behavior of gliclazide from its solid dispersion with polyethylene glycol 6000. In this work, a solid dispersion of gliclazide with polyethylene glycol was prepared by the fusion method. In vitro dissolution study of gliclazide, its physical mixture and solid dispersion were carried out to demonstrate the effect of PEG 6000. Analytical techniques of FT-IR spectroscopy, differential scanning calorimetry and X-ray diffractometry were used to characterize the drug in the physical mixtures and solid dispersions. The dissolution studies of solid dispersion and physical mixture showed greater improvement compared to that of the pure drug. The mechanisms for increased dissolution rate may include reduction of crystallite size, a solubilization effect of the carrier, absence of aggregation of drug crystallites, improved wettability and dispersbility of the drug from the dispersion, dissolution of the drug in the hydrophilic carrier or conversion of drug to an amorphous state. The FT-IR spectra suggested that there was no interaction between gliclazide and PEG 6000 when prepared as a solid dispersion. DSC and XRD study indicated that the drug was converted in the amorphous form.

O presente trabalho foi realizado com o objetivo de estudar o comportamento in vitro da dissolução da gliclazida a partir da sua dispersão sólida com polietileno glicol 6000. Neste trabalho, as dispersões sólidas de gliclazida com polietileno glicol foram preparadas pelo método de fusão. Os estudo de dissolução in vitro da gliclazida, na mistura física e nas dispersões sólidas foram realizados para demonstrar o efeito de PEG 6000. Técnicas analíticas como espectroscopia FT-IR, calorimetria diferencial de varredura e difração de raios-X foram empregadas para caracterizar o fármaco nas misturas físicas e nas dispersoes sólidas. Os estudos de dissolução demonstraram maior melhoria. Os mecanismos para aumentar a velocidade de dissolução podem incluir a redução do tamanho dos cristais, a solubilização do carreador, a ausência de agregação dos cristais do fármaco, a melhoria da molhabilidade e dispersibilidade do fármaco a partir da dispersão, a dissolução do fármaco no carreador hidrofílico ou conversão da forma cristalina do fármaco para estado amorfo. Os espectros de FT-IR sugeriram que não houve interação entre gliclazide PEG 6000 e na sua combinação. Os estudos de DSC e DRX indicaram que o fármaco foi convertido para a forma amorfa.

Preparation and characterization of gliclazide-polyethylene glycol 4000 solid dispersions.

The objective of the present investigation was to study the effect of polyethylene glycol 4000 (PEG 4000) on in vitro dissolution of gliclazide from solid dispersions. Initial studies were carried out using physical mixtures of the drug and carrier. Solid dispersions were prepared by the melting or fusion method.Phase and saturation solubility study, in vitro dissolution of pure drug, physical mixtures and solid dispersions were carried out. PEG was found to be effective in increasing the dissolution of gliclazide in solid dispersions when compared to pure drug. FT-IR spectroscopy, differential scanning calorimetry and X-ray diffractometry studies were carried out in order to characterize the drug in the physical mixtures and solid dispersions. Dissolution enhancement was attributed to decreased crystallinity of the drug and to the wetting and solubilizing effect of the carrier from the solid dispersions of gliclazide. In conclusion, dissolution of gliclazide can be enhanced by the use of hydrophilic carrier.