Lignin as a Bioactive Additive in Chlorzoxazone-Loaded Pharmaceutical Tablets

In the present work, the application of lignin (LIG) as a bioactive additive for the preparation of drug-loaded tablets by direct compression has been studied, and its influence on the release of chlorzoxazone (CLZ) from the hydrophilic matrices has been followed. In hydrophilic matrices, the excipients Kollidon^® SR (KOL) and chitosan (CHT) have been used in various amounts and tested in the preparation of 500 mg tablets. They were used as matrix-forming agents, and their influence on the flow and the compressibility properties as well as their effect on the pharmaco-chemical characteristics of the matrix tablets have been studied. Based on the initial evaluation of the pharmaco-technical analysis, pharmaco-chemical characteristics, and in vitro release profile, three matrix tablet formulations (FLa, FLb, and FLc) were selected and further tested. They were evaluated through Fourier-transform infrared spectrometry (FTIR), X-ray diffraction (XRD), thermogravimetry (TG), differential scanning calorimetry (DSC), and in vitro dissolution tests. The three formulations were comparatively studied regarding the release kinetics of active substances using in vitro release testing. The in vitro kinetic study reveals a complex release mechanism occurring in two steps of drug release. The first one is a burst effect that occurs within the first 0-2 h, involving a rapid release of the majority of the drug in a short time, followed by the second step as a prolonged release of the drug, which is relatively constant with a fixed rate over the next 2-36 h. Two factors have been calculated to assess the release profile of chlorzoxazone: f1-the similarity factor and f2-the difference factor together with the correlation coefficient R². Comparing their values, the three optimal formulations have been selected, containing 55 mg LIG (FLa), 60 mg LIG (FLb), or 65 mg LIG (FLc), confirming that LIG next to KOL and CHT influenced the release characteristics of the matrix tablets. Due to the presence of lignin in the matrix of the three formulations, FLa, FLb, and FLc tablets with CLZ, the antioxidant activity has improved. The antioxidant activity of FLc was found to be 21.36% ± 1.06 greater than that of FLa and FLb. The tablets FLa, FLb, and FLc also presented higher antimicrobial activity against <i>Staphylococcus aureus</i>, <i>Escherichia coli</i>, <i>Candida albicans</i>, and colistin-resistant <i>Klebsiella</i> spp. The higher the concentration of LIG in the matrix (FLc), the higher the antimicrobial activity. By using LIG, the drug dose could be decreased. It can be concluded that lignin can be used as a multifunctional pharmaceutical bioactive additive/excipient for tablets. Its interesting properties have been proven, and its use as a pharmaceutical active additive should be exploited for different applications.