In Vitro Evaluation of Lornoxicam Liquitablets: Permeability, Anti-Inflammatory Action, Cytotoxicity, and Stability

Lornoxicam (LXM) is a potent non-steroidal anti-inflammatory drug (NSAID), characterised by low aqueous solubility, which limits its oral bioavailability and is frequently associated with gastrointestinal adverse effects. The liquitablet, prepared by blister moulding combined with freeze-drying, was previously shown to significantly improve LXM dissolution. The present study extends that work by comprehensively evaluating biopharmaceutical and pharmacological performance through in vitro permeability testing, cytotoxicity, anti-inflammatory efficacy, and long-term physicochemical stability.

Dissolution profiling was performed in a pH 1.2 medium. Drug release data were fitted to zero-order, first-order, Higuchi, Hixson-Crowell, Korsmeyer-Peppas and Weibull models. Apparent permeability coefficients (Papp) and flux ratios were determined using a horizontal diffusion cell system together with Parallel Artificial Permeability Assays (PAMPA). Cytotoxicity was evaluated using an MTT assay in Caco-2 cells in clinically relevant concentrations. Anti-inflammatory activity was evaluated in Caco-2 cells induced with lipopolysaccharide (LPS) by quantifying the expression of cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6) mRNA using polymerase chain reaction (qRT-PCR). Stability was assessed over 12 months at (25°C/60% RH), the assessment focused on drug content, solid‑state characterisation, and dissolution profiling.

LXM liquitablets dissolution fitted both Weibull and Korsmeyer-Peppas models, and exhibited a statistically significant increase in Papp compared to pure LXM, with an efflux ratio below 2.0, and maintained Caco-2 cell viability above 70% cytotoxicity threshold at all therapeutic concentrations. It induced a marked downregulation of COX-2 and IL-6 mRNA expression, with high COX-2 attenuation relative to pure LXM, thereby confirming that the liquitablet retains anti-inflammatory activity. Stability data showed no significant changes in drug content (≥ 96%), solid-state characteristics, or dissolution profile.

LXM liquitablets show improved diffusion, biocompatibility, anti-inflammatory action, and long-term stability, providing strong biopharmaceutical support for clinical and regulatory development.