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.

Efeito da massa molar do acetobutirato de celulose e da adição de poli(3-hidroxibutirato) sobre as características das microesferas e o prolongamento da liberação do cetoprofeno / Effects of cellulose acetate butyrate molar weight and addition of poly(3-hydroxybutyrate) on microsphere morphology and ketoprofen prolonged release

No presente trabalho, foram elaboradas microesferas de acetobutirato de celulose (ABC) contendo cetoprofeno com o objetivo de prolongar a liberação do fármaco. Utilizou-se a técnica de emulsão e evaporação do solvente, variando-se os seguintes parâmetros: massa molar do ABC e a adição ou não de poli(3-hidroxibutirato) (PHB), segundo um planejamento fatorial 22. Maiores eficiências de encapsulação do cetoprofeno foram obtidas quando utilizado ABC com maior massa molar e a adição do PHB levou a uma diminuição do percentual de fármaco encapsulado. Todas as formulações originaram partículas esféricas, com cristais de fármacos aderidos à superfície externa e matriz polimérica porosa quando adicionado o PHB. Os perfis de liberação in vitro indicaram que o aumento da massa molar do ABC levou a uma diminuição do percentual de fármaco inicialmente liberado e a um prolongamento de sua liberação. Por outro lado, a adição do PHB acelerou a liberação do cetoprofeno a partir das microesferas.

In the present study, cellulose acetate butyrate (CAB) microspheres containing ketoprofen were produced, with the objective of prolonging its release. The emulsion/solvent evaporation technique was used to make the spheres, varying the parameters (1) CAB molecular weight and (2) addition or not of poly(3-hydroxybutyrate) [PHB], to optimize drug encapsulation, following a 2² factorial design. Higher ketoprofen encapsulation efficiency was obtained when higher molecular weight CAB was used, while the addition of PHB caused a decrease in the percentage of encapsulated drug. All the preparations produced spherical particles, with drug crystals adhering to the external surface, and a porous polymer matrix when PHB was used. The in vitro release profiles indicated that lowering the CAB molecular weight led to a decrease in the drug initially released and a prolonged release. On the other hand, the addition of PHB accelerated the release of the ketoprofen from the microspheres.