Production of a new platform based on fumed and mesoporous silica nanoparticles for enhanced solubility and oral bioavailability of raloxifene HCl

Abstract

The purpose of the present study was to compare mesoporous and fumed silica nanoparticles (NPs) to enhance the aqueous solubility and oral bioavailability of raloxifene hydrochloride (RH). Mesoporous silica NPs (MSNs) and fumed silica NPs were used by freeze-drying or spray-drying methods. MSNs were obtained with different ratios of cetyltrimethylammonium bromide. Saturation solubility of the NPs was compared with the pure drug. The optimised formulation was characterised by scanning electron microscopy (SEM), X-ray diffraction (XRD) and differential scanning calorimetry. The pharmacokinetic studies were done by oral administration of a single dose of 15 mg/kg of pure drug or fumed silica NPs of RH in Wistar rats. MSNs enhanced the solubility of RH from 19.88 ± 0.12 to 76.5 μg/ml. Freeze-dried fumed silica increased the solubility of the drug more than MSNs (140.17 ± 0.45 μg/ml). However, the spray-dried fumed silica caused about 26-fold enhancement in its solubility (525.7 ± 93.5 μg/ml). Increasing the ratio of silica NPs enhanced the drug solubility. The results of XRD and SEM analyses displayed RH were in the amorphous state in the NPs. Oral bioavailability of NPs showed 3.5-fold increase compared to the pure drug. The RH loaded fumed silica NPs prepared by spray-drying technique could more enhance the solubility and oral bioavailability of RH.

Optimization of mirtazapine loaded into mesoporous silica nanostructures via Box-Behnken design: in-vitro characterization and in-vivo assessment

“…According to the polynomial equation, the saturation aqueous solubility is affected negatively by the drug/MSNs ratio, whereas decreasing the drug ratio leads to an increase in the aqueous solubility of MRT. The Mirtazapine-MSNs ratio of 66.66% showed the lowest aqueous solubility, whereas the loading ratio of 33.33% showed the highest aqueous solubility (Varshosaz et al., 2019 ) ( Figure 2 ). This is assumed to the fact that most drugs changed from crystalline to amorphous state with lower lattice energy after being encapsulated into MSNs with a low drug ratio, resulting in increased drug solubility (T. Li et al., 2019 ).…”

“…Samples of plain MRT, SBA-15, optimized MRT-SBA-15 and physical mixture of MRT and SBA-15 were filled into the holder and irradiated with monochromatized Cu Kα radiation at 30 kV and 30 mA. The step size within an angle of (2θ) over a range of 5°-50°, using the X-ray diffractometer (Scintage XDS 2000 diffractometer, USA) (Varshosaz et al., 2019 ).…”

Design of mirtazapine solid dispersion with different carriers’ systems: optimization, in vitro evaluation, and bioavailability assessment

“…The samples were placed in the holder before being exposed to monochromatized CuK radiation at 30 kV and 30 mA. The step size within an angle of 2 θ is over a range of 5–50° [ 16 ].…”

Formulation and Evaluation of a Self-Microemulsifying Drug Delivery System of Raloxifene with Improved Solubility and Oral Bioavailability

“…Improving the solubility and dissolution rate of RLX will overcome its poor oral absorption. Various formulations, including lecithin–chitosan nanoparticles [ 15 ], solid dispersion [ 16 , 17 ], inclusion complexes [ 18 ], micro- and nano-emulsions [ 14 , 19 ], nanostructured lipid carriers [ 20 , 21 ], dry suspensions [ 22 ], mesoporous silica nanoparticles [ 23 ], phospholipid complexes [ 24 ], and polymeric nanoparticles [ 25 , 26 ], have been investigated to enhance the solubility and oral bioavailability of RLX. However, oral absorption of RLX remains low and continued efforts are required to improve its oral bioavailability.…”