Developing Composition and Technology of Ethylthiobenzimidazole Fumarate Matrix Tablets According to Specified Release Profile

INTRODUCTION. Ethylthiobenzimidazole fumarate (ETBIF) is a new actoprotector and adaptogenic active pharmaceutical ingredient (API). ETBIF was found to be effective given in short intervals; side effects related to ETBIF stomach solubility are known. Therefore, it is essential to develop a matrix dosage form with a specific release profile that can neutralize these side effects, prolong dosing intervals, and increase treatment compliance. AIM. This study aimed to develop composition and production technology of ETBIF matrix tablets in accordance with a specified release profile (total release within 12 hours; not more than 50% of ETBIF released in acidic environment within the first two hours; the rest evenly released over the next 10 hours in the intestine-simulating environment). MATERIALS AND METHODS. The study examined ETBIF (API) as well as hydroxypropylmethylcellulose (hypromellose) and ethyl cellulose-based matrix ETBIF tablets. Mechanical properties of the tablets were examined, in particular hardness and friability. ETBIF release profiles were studied in different phosphate buffer solutions (pH 1.2, 4.5, and 6.8) using a dissolution tester and UV spectrometry. RESULTS. The authors studied ETBIF release kinetics from matrix systems with various matrix-forming components of different origin. Hypromellose-based compounds enabled prolonged ETBIF release (90% after 12 h). Ethyl cellulose compounds showed 60 to 90% release, with API mostly releasing in acidic environment. Adding an acid does not affect ETBIF release from matrix tablets. CONCLUSIONS. A composition of matrix tablets has been developed that meets the specified release profile. Hypromellose-based tablets showed the most complete and uniform release of the substance in an environment simulating gastrointestinal tract. Adding an acid does not affect ETBIF release from matrix tablets, despite its increased solubility in the acidic environment.