ARTICLE | doi:10.20944/preprints202301.0170.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: biopharmaceutical; nephroprotective; oral absorption; self-micellizing solid dispersion; thymoquinone.
Online: 10 January 2023 (03:09:17 CET)
The present study was designed to develop a self-micellizing solid dispersion (SMSD) containing Thymoquinone (TQM), a phytonutrient obtained from Nigella sativa seeds, aiming to improve its biopharmaceutical and nephroprotective functions. The apparent solubility of TQM in polymer solutions was used to choose an appropriate amphiphilic polymer that could be used to make an SMSD system. Based on the apparent solubility, Soluplus® was chosen as an appropriate carrier, and mixing with TQM, SMSD-TQM with different loadings of TQM (5–15%) was made by solvent evaporation and freeze-drying techniques, respectively, and the formulations were optimized. The optimized SMSD-TQM was evaluated in terms of particle size distribution, morphology, release characteristics, pharmacokinetic behavior, and nephroprotective effects in a rat model of acute kidney injury. SMSD-TQM significantly improved the dissolution characteristics (97.8%) of TQM in water within 60 min. Oral administration of SMSD-TQM in rats exhibited a 4.9-fold higher systemic exposure than crystalline TQM. In a cisplatin-induced (6 mg/kg, i.p.) acute kidney-damaged rat model, oral SMSD-TQM (10 mg/kg) improved the nephroprotective effects of TQM based on the results of kidney biomarkers and histological abnormalities. These findings suggest that SMSD-TQM might be efficacious in enhancing the nephroprotective effect of TQM by overcoming biopharmaceutical limitations.
ARTICLE | doi:10.20944/preprints202211.0372.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: biopharmaceutical; nephroprotective; oral absorption; self-micellizing solid dispersion; thymoquinone.
Online: 21 November 2022 (04:43:27 CET)
Nigella sativa's thymoquinone (TQM), a water-insoluble phytonutrient exhibits nephroprotective effects. This study intends to develop a self-micellizing solid dispersion (SMSD) of TQM for better biopharmaceutical and nephroprotective performance. Soluplus®-based SMSD of TQM was created and tested for physicochemical properties, solubility, and pharmacokinetics in rats. Plasma creatinine, blood urea nitrogen (BUN), nephrotoxic indicators, and oxidative stress biomarkers were also tested. During SMSD preparation, TQM was found amorphous, boosting solubility. Minimal band changes between TQM and Soluplus® indicate insignificant drug-carrier interactions. SMSD-TQM generated fine micelles in water, improving TQM's solubility by 97.8% in 60 min. SMSD-TQM was 4.9 times more bioavailable orally in rats than crystalline TQM. In a rat model of acute renal damage by cisplatin (6 mg/kg, i.p.), SMSD-TQM (10 mg-TQM/kg, p.o.) reduced blood creatinine and BUN by 56% and 63.2%, respectively. These findings imply that SMSD-TQM may be a potent dosage option for enhancing TQM's nutrient value.