Fabrication, In Vitro and In Vivo Evaluation of Non-Ordered Mesoporous Silica-Based Ternary Solid Dispersions for Enhanced Solubility of Flurbiprofen

Abstract

The aim of this study was to improve the solubility and prevent the ulcerogenic effect of flurbiprofen. Initially, binary and ternary solid dispersions (BSDs and TSDs) of flurbiprofen were prepared by using non-ordered mesoporous silica and gelucire. After preformulation testing (solubility, flow properties, % yield, and entrapment efficiency), four formulations were selected for further detailed studies. Solid-state characterization of optimized formulations (S1, S6, S7, and S12) showed successful drug incorporation in the solid dispersion at the molecular state without any noticeable interactions. The in vitro solubility and release study showed an increase in solubility and 98–100% of drug release in 30–45 min. The in vivo gastro-protective effect of the optimized formulations containing flurbiprofen and silica (1:1) with 25% w/w gelucire (S6 and S12) showed a reduction in the gastric lesion index (GLI) after four days of treatment. Moreover, histological images of the stomach lining (S6 and S12) illustrated normal epithelial cells and a partially protected mucosal membrane. Thus, TSD exhibited a significant increase in solubility and the dissolution rate and reduced the gastric ulceration. Therefore, TSDs are dubbed as efficacious carriers to enhance the bioavailability of flurbiprofen while simultaneously reducing its side effects.

Enhanced Solubility and Biological Activity of Dexibuprofen-Loaded Silica-Based Ternary Solid Dispersions

“…It was observed that free-flowing dispersions were obtained with lipid carriers up to 40%, beyond which a sticky and agglomerated mass was obtained, thus hindering processing. Similar trends have been reported for TSDs based on gelucire [ 27 ]. For hydrophilic carriers, drug solubility showed an increasing trend with a higher concentration of carrier, which may have been due to the improved wetting and solubilizing nature of surfactants [ 22 ].…”

“…In the case of S1, S18, and S23, the absorption peaks of Dex were shifted from 1697 to 1704.17, 1732.16, and 1732.09 cm −1 . This is possibly due to the weak interaction of Dex with the mesoporous surface, which is reversible in nature, as mentioned in the literature [ 27 , 36 , 37 ].…”

“…This decrease in solubility was due to the use of a higher weight ratio of ternary carriers, which provided a coating for the slow release of drug [ 33 ]. The syloid coating also contributes to the gastroprotective effect of ternary carriers [ 27 ]. The drug content of TSDs ranged from 47% to 97%.…”

“…The literature supports our findings, whereby drug confinement to silica pores prevents recrystallization of the drug, resulting in powdered dispersions. This helps to improve the solubility of the drug [ 27 , 43 , 44 ].…”

“…An arbitrary score (AS) was given to ulcers: “0” for no lesion or ulcer, “0.5” for one or more ulcers with length less than 1 mm, “1” for ulcers/lesions with length 1–2 mm, and “2” for ulcers/lesions with length >2 mm. The gastric lesion index (GLI) was calculated as follows [ 27 ]: Gastric lesion index = AS × No. of lesions.…”