Soluplus®-Based pH-Modulated Solid Dispersions of Lornoxicam for Enhanced Oral Bioavailability

Abstract

Lornoxicam, a potent nonsteroidal anti-inflammatory drug (NSAID), suffers from poor aqueous solubility, leading to limited dissolution and variable bioavailability. It is a nonsteroidal anti-inflammatory medication (NSAID) that is commonly recommended to treat rheumatoid arthritis, osteoarthritis, and postoperative pain. This study aimed to enhance its solubility and oral performance by developing pH-modulated solid dispersions with Soluplus® as a carrier and sodium bicarbonate as a pH modifier. A Central Composite Design (CCD) was employed with Design-Expert® software (version 13.0) to optimise the solid dispersion formulation. DSC thermograms were recorded on a Mettler Toledo instrument. Morphology was analysed using a CamScan Maxim-2000 SEM operated at 20 kV. Adult Wistar rats (220–250 g, 10–15 weeks old) were maintained under controlled environmental conditions (25 ± 2 °C, 12-h light/dark cycle, 55 ± 5% RH) with free access to food and water. Solid dispersions were prepared via solvent evaporation and optimised using a Central Composite Design approach. The optimised batch (F7) was characterised through FTIR, DSC, PXRD, and SEM to confirm drug–excipient compatibility, amorphisation, and morphological changes. Three immediate-release tablet formulations (F1–F3) were then developed using PROSOLV® EASYtab SP. The optimised solid dispersion (F7) exhibited significantly improved solubility (1.73 mg/mL). Among the prepared tablets, F1 demonstrated superior properties, including 97.45% drug content, 40-second disintegration time, and 98.54% drug release. Pharmacokinetic evaluation in Wistar rats revealed enhanced bioavailability for F1 (AUC₀–∞ = 18,270 ng·h/mL; Cmax = 3,446 ng/mL) compared to the marketed formulation, Lorsaid SP® (AUC₀–∞ = 17,814.5 ng·h/mL; Cmax = 3,198 ng/mL). Accelerated stability studies (40 °C/75% RH, 30 days) further confirmed the formulation’s stability. ANOVA results (F-values of 9.51 for Y1 and 18.10 for Y2) validated the contribution of both independent variables to the responses. Precision indicators such as standard deviation (0.0321 for Y1 and 1.96 for Y2) and coefficient of variance (0.66% for Y1 and 0.58% for Y2) confirmed experimental reproducibility. The Soluplus®-based pH-modulated solid dispersion strategy effectively improved the solubility, dissolution, and pharmacokinetic performance of Lornoxicam. The optimised F1 tablets demonstrated promising potential for clinical application by offering rapid disintegration, enhanced bioavailability, and good stability. These findings create a strong formulation strategy for medications with low water solubility, such as Lornoxicam, ensuring enhanced oral delivery by logical excipient selection and formulation optimisation. GRAPHICAL ABSTRACT