Investigation of the Dissolution Profile of Gliclazide Modified-Release Tablets Using Different Apparatuses and Dissolution Conditions.

In the absence of an official dissolution method for modified-release tablets of gliclazide, dissolution parameters, such as apparatuses (1, 2, and 3), rotation speeds, pH, and composition of the dissolution medium were investigated. The results show that although the drug presents a pH-mediated solubility (pH 7.0 > 6.8 > 6.4 > 6.0 > 5.5 > 4.5), the in vitro release of the studied tablets was not dependent on this parameter, despite of the apparatus tested. On the other hand, the rotation speed demonstrated a greater influence (100 rpm >50 rpm). Using similar hydrodynamic conditions, the three different apparatuses were compared in pH 6.8 and provided the following trend: apparatus 1 at 100 rpm >2 at 50 rpm ≈3 at 10 dpm. As a complete, but slow release is expected from modified-release formulations, apparatus 2, in phosphate buffer pH 6.8 and 100 rpm, were selected as the optimized dissolution method. In comparison to apparatus 1 under the same conditions, the paddle avoids the stickiness of formulation excipients at the mesh of the basket, which could prejudice the release of gliclazide. Results obtained with biorelevant medium through the developed dissolution method were similar to the buffer solution pH 6.8. The application of the optimized method as a quality control test between two different brands of gliclazide modified-release tablets showed that both dissolution profiles were considered similar by the similarity factor (f2 = 51.8). The investigation of these dissolution profiles indicated a dissolution kinetic following first-order model.

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.

Ensayo clínico cruzado y randomizado de biodisponibilidad relativa de dos formulaciones de gliclazida comprimidos de 30 mg de liberación sostenida, administrados en dosis única a voluntarios sanos / Clinical trial randomized crossover relative bioavailability of two formulations of gliclazide of 30 mg tablets administered sustained release single dose to healthy volunteers

El objetivo principal consistió en conocer la biodisponibilidad relativa de una nueva formulación de gliclazida (Gliclazida comprimidos de liberación sostenida Laboratorios Genven) con respecto a la formulación de Laboratorios Servier tomada como referencia, y establecer su bioequivalencia de acuerdo a los criterios recomendados por las autoridades sanitarias. Se hizo asimismo una valoración de la tolerancia de ambos preparados. Se diseñó un estudio abierto, randomizado, cruzado, dos periodos, con siete días de lavado, con 12 voluntarios sanos de ambos sexos, entre 21 y 55 años, quienes ingirieron un comprimido del fármaco en estudio: GLICLAZIDA comprimidos DE LIBERACIÓN SOSTENIDA de 30 mg, fabricados por Laboratorios GENVEN, o del Fármaco control: GLICLAZIDA comprimidos DE LIBERACIÓN SOSTENIDA de 30 mg, fabricados por Laboratorios SERVIER, comercializados en Venezuela con el nombre de DIAMICROM MR®. La bioequivalencia se determinó con los parámetros farmacocinéticos de área bajo la curva AUC (0-t), AUC 0-∞ y concentración máxima (Cmax). Con ambas formulaciones se inicia la aparición en plasma de niveles cuantificables desde los 30 minutos, ambos productos alcanzan su Cmax alrededor de las 12 horas, con una Cmax para Gliclazida de Laboratorios Genven (GL) de 558.57 +/- 191.43 ng/mL y para Gliclazida marca Diamicrón MR® (GD) de 514.56 +/- 140.94 ng/mL sin diferencias significativas (P= 0.66). En cuanto al área debajo de la curva (AUC), encontramos valores de AUC 0-t de 539.68 +/- 210.75 ng/mL/h para GL y de 585.07 +/- 240.66 ng/mL/h para GD sin diferencias significativasentre estas (P= 0.91). Para el AUC0-∞ los valores fueron de 569.14 +/- 216,95 ng/mL/h para GL y de 616.93 +/- 244.37ng/mL/h para GD (P= 0.71)

The main objective was evaluated the relative bioavailability of a new formulation of gliclazide (gliclazide sustained release tablets Genven Laboratories) regarding the formulation of Laboratoires Servier taken as a reference and establish their bioequivalence according to the criteria recommended by health authorities. It was also an assessment of tolerance of both preparations. We performed a study open, randomized, crossover two periods, with seven days of washing, with 12 healthy volunteers of both sexes, between 21 and 55 years who ate a pill in drug study: GLICLAZIDE Liberation sustainable tablets 30 mg, manufactured by Genven Laboratories or drug control: GLICLAZIDE Liberation sustainable tablets 30 mg, manufactured by Servier Laboratories in Venezuela, marketed under the name DIAMICROM MR®. The bioequivalence was determined with the pharmacokinetic parameters of area under the curve AUC (0-t), AUC 0-∞ and maximum concentration (Cmax). With both formulations began appearing on plasma levels quantifiable from the 30 minutes, both product’s reach their Cmax around 12 hours, with a Cmax for gliclazide Genven Laboratory (GL) from 558.57 +/- 191.43 ng/mL and Gliclazide Diamicron MR® (GD) from 514.56+/-140.94 ng/mL without significant differences (P= 0.66). As for the area under the curve (AUC) values were found AUC 0-t 539.68 +/-210.75 ng/mL/h for GL and 585.07 +/- 240.66 ng/mL/h for GD no significant differences between these (P= 0.91). For AUC 0-∞ values were 569.14 +/- 216.95 ng/mL/h for GL and 616.93 +/- 244.37 ng/mL/h for GD (P= 0.71)