Investigation of the possibility of obtaining prolonged-release solid dispersions of trimetazidine dihydrochloride

I n t r o d u c t i o n . Prolonged-release formulations are designed to minimize the problems of traditional dosage forms, such as fluctuations in plasma concentration of a drug and the need for frequent dosing. Trimetazidine dihydrochloride (TMD), an antianginal drug, is a suitable candidate to develop prolonged-release formulations, although this is a rather challenging task due to its high water solubility.
A i m . To investigate the possibility of preparing prolonged-release solid dispersions (SDs) of TMD using different ratios of Eudragit® RSPO or POLYOX™ WSR coagulant as polymers that prolong the drug release.
M a t e r i a l s a n d m e t h o d s . SD variants with active pharmaceutical ingredient (API) to polymer ratios of 1:2, 1:4, and 1:8 were prepared by the solvent (isopropanol) evaporation method, and were evaluated on such characteristics as: API content uniformity, flowability and compressibility, weight loss on drying, dissolution. X-ray diffraction analysis and microscopy were also performed.
R e s u l t s . The API was evenly distributed in the SDs prepared, and its content ranged from 96,91 to 103,16%. The weight loss on drying was 1,08–2,24%, the flowability and compressibility ranged from good to excellent. The dissolution rate was reduced due to an increase in the proportion of polymer, with the possibility of extending the drug release to 17 h using Eudragit® RSPO. However, it was not possible to obtain а prolonged-release profile in SDs prepared with POLYOXTM WSR coagulant. The X-ray diffraction analysis and microscopic sexamination showed the formation of SDs, in which the API is dispersed within the polymer.
C o n c l u s i o n . By the solvent evaporation method using a suitable polymer in suitable proportions SD of water-soluble API – prolonged-release TMD – can be obtained with the characteristics required for further pharmaceutical investigation.

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