ВПЛИВ РОЗЧИННИХ НАПОВНЮВАЧІВ ІЗ РІЗНИМ РОЗМІРОМ ЧАСТОК НА КІНЕТИКУ ВИВІЛЬНЕННЯ ТРИМЕТАЗИДИНУ ДИГІДРОХЛОРИДУ IN VITRO З МАТРИЧНИХ ТАБЛЕТОК
Authors: Могилюк В. В. , Давтян Л. Л. 
Published: September 2015

<p><strong>EFFECT OF SOLUBLE DILUENTS WITH DIFFERENT PARTICLE SIZE ON DISSOLUTION PROFILE OF TRIMETAZIDINE DIHYDROCHLORIDE FROM MATRIX TABLETS</strong></p><p><strong>V. V. Mohylyuk, L. L. Davtian </strong></p><p>ShupykNationalMedicalAcademyof Postgraduate Education, Kyiv</p><p><strong>Summary: </strong>The effect of soluble diluent lactose monohydrate and sorbitol with average particle size 11, 17, 251 and 110, 299, 531 µm, respectively, on dissolution profile of trimetazidine dihydrochloride model substance from matrix tablets with insoluble and unswellable Ethocel 10, insoluble and swellable Kollidon SR, soluble and swellable Methocel K4M as matrix formers was investigated. The effect of soluble diluents particle size on drug release from matrix tablets with different matrix formers was established and explained.<strong></strong></p><p><strong>Key words: </strong>matrix tablet, Ethocel, Kollidon SR, Methocel K, sorbitol, lactose.</p><p><strong>Introduction. </strong>Oral matrix tablets are the modern dosage forms using which could be achieved desirable in vitro release kinetics of active pharmaceutical ingredient (API) and correspondent in vivo concentration level. That’s why the study of factors that affect in vitro dissolution release of API is an actual task and the effect of diluents particle size is one of these factors. There are two main types of matrix systems with different mechanism of soluble components release: with soluble matrix former that is forming the gel layer on the surface of matrix and with insoluble matrix former. The aim of this study is to investigate the effect of diluent’s particle size on dissolution profile of trimetazidine dihydrochloride from matrix tablets with insoluble and unswellable Ethocel 10, insoluble and swellable Kollidon SR, soluble and swellable Methocel K4M as matrix formers.</p><p><strong>Methods.</strong> Particle size distribution measurement by the laser scattering method, tablet manufacturing using direct compression method for more predictable tablet structure, dissolution test and matrix tablets structure evaluation by optical microscopy were used for experiment.</p><p><strong>Results and discussion.</strong> On a more detailed level tablet components form clusters. These clusters have a specific structure that is depending on the number, size, shape, volume ratio of the components and the method of tablets manufacture. Soluble sorbitol and less soluble lactose monohydrate were used for experiment. The drug release from Ethocel 10 matrix was decreased with diluents particle size increasing. The drug release from Kollidon SR matrix was decreased with soluble diluents particle size increasing from 17 to 110 µm and follow particle size increasing from 110 to 513 µm almost hadn’t affect. Diluents particle size almost hadn’t effect on drag release from Methocel K4M matrix tablets too. The effect of diluents particle size increasing on release from insoluble unswellable Ethocel 10 and insoluble swellable Kollidon SR matrices could be explained from position of percolation theory by more isolated clusters formation and porosity decreasing. The almost absence of diluents particle size effect on drug release from soluble swellable Methocel K4M matrix could be explained by diffusion mechanism predominance. The release of trimetazidine dihydrochloride (340 g/ml) from Ethocel 10, Kollidon SR and Methocel K4M matrix tablets was faster when used sorbitol (&gt;4000 g/ml) than lactose monohydrate (210 g/ml). This result is consistent with the higher solubility of sorbitol in comparison with lactose monohydrate.</p><p><strong>Conclusions.</strong> Decreasing of trimetazidine dihydrochloride dissolution kinetics from Ethocel 10 matrix tablets with lactose and sorbitol particle size increasing was established. The dissolution kinetics from Kollidon SR matrix tablets was decreased with soluble diluent particle size increasing from 17 to 110 µm, but sorbitol particle size increasing from 110 to 513 µm had no effect on dissolution profile. Particle size of soluble diluents had no significant effect on dissolution kinetics from Methocel K4M matrix tablets. The dissolution kinetics from tablets with Ethocel 10, Kollidon SR and Methocel K4 as matrix formers was decreased with diluent solubility decreasing.</p>