| Summary: | In the current study, matrices of losartan potassium were formulated with two different polymers (Ethocel 10 premium and Ethocel 10FP premium), along with a filler and a lubricant, at different drug-to-polymer <i>w</i>/<i>w</i> ratios (10:3, 10:4, and 10:5). The matrices were tested by the direct compression method, and their hardness, diameter, thickness, friability, weight variation, content uniformity, and in vitro dissolution tests were assessed to determine 24-h drug release rates. The matrices with Ethocel 10 FP at a 10:4 ratio exhibited pseudo-zero-order kinetics (n-value of 0.986), while the dissolution data of the test matrices and reference tablets did not match. The new test-optimized matrices were also tested in rabbits, and their pharmacokinetic parameters were investigated: half-life (11.78 ± 0.018 h), Tmax (2.105 ± 1.131 h), C<sub>max</sub> (205.98 ± 0.321 μg/mL), AUC<sub>o</sub> (5931.10 ± 1.232 μg·h/mL), AUC<sub>o-inf</sub> (7348.46 ± 0.234 μg·h/mL), MRT<sub>o-48h</sub> (17.34 ± 0.184 h), and Cl (0.002 ± 0.134 mL/min). A correlation value of 0.985 between the in vitro and in vivo results observed for the test-optimized matrices was observed, indicating a level-A correlation between the percentage of the drug released in vitro and the percentage of the drug absorbed in vivo. The matrices might improve patient compliance with once-a-day dosing and therapeutic outcomes.
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