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

Abstract

Employment of mesoporous silica nanostructures (MSNs) in the drug delivery field has shown a significant potential for improving the oral delivery of active pharmaceutical products with low solubility in water. Mirtazapine (MRT) is a tetracyclic antidepressant with poor water solubility (BCS Class II), which was recently approved as a potent drug used to treat severe depression. The principle of this research is to optimize the incorporation of Mirtazapine into MSNs to improve its aqueous solubility, loading efficiency, release performance, and subsequent bioavailability. The formulation was optimized by using of Box-Behnken Design, which allows simultaneous estimation of the impact of different types of silica (SBA-15, MCM-41, and Aluminate-MCM-41), a different drug to silica ratios (33.33%, 49.99%, and 66.66%), and different drug loading procedures (Incipient wetness, solvent evaporation, and solvent impregnation) on the MRT loading efficiency, aqueous solubility and dissolution rate. The optimized formula was achieved by loading MRT into SBA-15 at 33.33% drug ratio prepared by the incipient wetness method, which displayed a loading efficiency of 104.05%, water solubility of 0.2 mg/ml, and 100% dissolution rate after 30 min. The pharmacokinetic profile of the optimized formula was obtained by conducting the in -vivo study in rabbits which showed a marked improvement (2.14-fold) in oral bioavailability greater than plain MRT. The physicochemical parameters and morphology of the optimized formula were characterized by; gas adsorption manometry, scanning electron microscopy (SEM), polarized light microscopy (PLM), Fourier-transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and X-ray powder diffraction (XRPD).

The Exploitation of pH-Responsive Eudragit-Coated Mesoporous Silica Nanostructures in the Repurposing of Terbinafine Hydrochloride for Targeted Colon Cancer Inhibition: Design Optimization, In Vitro Characterization, and Cytotoxicity Assessment

“…SBA-15 has better loading efficiency than MCM-41. This might be because TER could distribute within the mesopores of SBA-15, which are larger and broader than MCM-41 pores, allowing TER to be entrapped into the pores easily and uniformly [ 6 ].…”

“…Table 1 outlines the desired goals for each dependent response. A high desirability value suggests that the response is compatible with its desired value [ 6 ]. Following that, the responses of the optimized formulation were re-examined, and the comparison took place between the experimental values and predicted values suggested by the D-optimal design.…”

“…The MSNs, a subset of inorganic nanoparticles, are becoming more commonly employed in medication delivery because of their reduced cytotoxicity at high concentrations compared to other inorganic nanomaterials [ 5 ]. According to substantial toxicological, safety, and epidemiological research, these biodegradable and biocompatible chemicals pose no environmental or health risk [ 6 ]. In addition, the MSNs are able to entrap a large amount of medication and then release it in a controlled release manner, making them commonly used in the production of sustained release systems that increase the drug’s therapeutic effectiveness and decrease the adverse effects [ 7 ].…”

Syringeable atorvastatin loaded eugenol enriched PEGylated cubosomes in-situ gel for the intra-pocket treatment of periodontitis: statistical optimization and clinical assessment

“…Moreover, the release profiles were further analyzed using the DDSolver software (Excel Add-in) by fitting the obtained data into different model equations to evaluate the release mechanism from different systems. The best-fit model was selected based on the highest correlation coefficient (r 2 ) (Rapalli et al., 2021 ; Musallam et al., 2022 ).…”

Ameliorating the Poor Dissolution Rate of Selexipag in Aqueous Acidic Conditions Following Confinement into Mesoporous Silica

“…18 Florek et al, 2017 and Musallam et al, 2022 stated that drug confinement into MSNs nanopores changes the crystal habit to the amorphous states and consequently augments the drug solubility. 8,19 As well, the presence of the entrapped drug inside the MSN pores may deter its recrystallization process upon storage. 20 Herein, we aimed to investigate the effectiveness of three forms of MSNs as nanocarriers for SXP to increase its dissolution rate.…”