Novel Bioequivalent Tablet of Solifenacin Succinate Prepared Using Direct Compression Technique for Improved Chemical Stability

Abstract

We designed a bioequivalent tablet form of solifenacin succinate (SOL) with an improved storage stability using a direct compression (DC) technique. An optimal direct compressed tablet (DCT) containing an active substance (10 mg), lactose monohydrate, and silicified microcrystalline cellulose as diluents, crospovidone as a disintegrant, and hydrophilic fumed silica as an anti-coning agent was constructed by evaluating the drug content uniformity, mechanical properties, and in vitro dissolution. The physicochemical and mechanical properties of the DCT were as follows: drug content 100.1 ± 0.7%, disintegration time of 6.7 min, over 95% release within 30 min in dissolution media (pH 1.2, 4.0, 6.8, and distilled water), hardness > 107.8 N, and friability ~0.11%. The SOL-loaded tablet fabricated via DC showed an improved stability at 40 °C and RH 75%, exhibiting markedly reduced degradation products compared to those fabricated using ethanol or water-based wet granulation or a marketed product (Vesicare®, Astellas Pharma). Moreover, in a bioequivalence study in healthy subjects (n = 24), the optimized DCT offered a pharmacokinetic profile comparable to that of the marketed product, with no statistical differences in the pharmacokinetic parameters. The 90% CIs for the geometric mean ratios of the test to the reference formulation for the area under the curve and the maximum drug concentration in plasma were 0.98–1.05 and 0.98–1.07, respectively, and satisfied the FDA regulatory criteria for bioequivalence. Thus, we conclude that DCT is a beneficial oral dosage form of SOL with an improved chemical stability.

Facile Access to Solifenacin Impurity K: One-Step Synthesis and an HPLC-MS Method for Its Determination

“…Regarding the impurities resulting from SFC degradation, the most commonly observed and identified impurity is N-oxide SFC (Impurity I), while studies on other impurities are still limited. Impurity K, resulting from the oxidation of SFC at the double benzylic position, was detected in SLN tablets by Do Hwan Kim & Co. and efforts have been made to minimize its presence by modifying the tablet fabrication process [15]. However, despite the presence of this impurity in the SLN tablets, only a complex synthetic route for its synthesis is reported in the literature [12].…”

“…13 C NMR (100.6 MHz, CDCl3): 19.5 (CH2, C5'), 24.6 (CH2, C8'), 25.4 (CH, C4'), 33.0 (CH2, C2), 42.5 (CH2, C1), 46.5 (CH2) and 47.4 (CH2) (C6' and C7'), 55. 6 (17), 98 (15), 81 (22), 77 (20), 55 (10). Ultraviolet spectra: Maxima at 212 and 254 nm.…”

Facile Access to Solifenacin Impurity K: One-Step Synthesis and an HPLC-MS Method for Its Determination

“…Regarding the impurities resulting from SFC degradation, the most commonly observed and identified impurity is N-oxide SFC (Impurity I), while studies on other impurities are still limited. Impurity K, resulting from the oxidation of SFC at the double benzylic position, was detected in SLN tablets by Do Hwan Kim & Co., and efforts have been made to minimize its presence by modifying the tablet fabrication process [14]. However, despite the presence of this impurity in the SLN tablets, only a complex synthetic route for its synthesis is reported in the literature [12].…”