Variable pore size of mesoporous silica in improving physical stability and oral bioavailability of insoluble drugs

Abstract

Mesoporous silica carriers are known to improve the solubility and bioavailability of poorly soluble Class II drugs. However, most mesoporous silica carriers available in the market have relatively low drug loading capacities. Therefore, it is essential to select the appropriate mesoporous silica carrier to control the particle size and form of poorly soluble drugs, as well as ensure efficient drug loading, particularly for drugs with large clinical dosages.

Highlights

• In vitro dissolution behavior of MSNs with different pore sizes was studied.
• Differences in the properties of MSNs and commercial carriers were compared.
• The solubilization mechanism of mesoporous carriers was investigated.
• Physical stability of MSN₁ and PVP K-30 under accelerated testing were compared.
• Pharmacokinetic studies of Fen@MSN₁ and commercial Lipanthyl® capsules were compared.

In this study, three types of dendritic mesoporous silica nanoparticles (MSNs) with similar particle sizes but different pore sizes (25 nm, 15 nm, and 5 nm) were prepared, which could be degraded by 80 % in simulated intestinal fluid at pH 6.8 over 7 days. Fenofibrate (Fen) was loaded into MSNs, commercial mesoporous silica excipients, and a traditional solid dispersion excipient (PVP K-30) using the solvent evaporation method. MSNs showed a higher drug loading efficiency (about 33 %) compared to commercial excipients. The drug-loaded systems increased the drug release rate and improved its hydrophilicity by reducing the contact angle. After loading, the specific surface area, pore volume, and pore size decreased.

Under accelerated test condition, the rigid structure of MSNs prevented drug crystallization, avoiding the aging issues seen with traditional solid dispersions like PVP K-30, and improved the drug’s long-term stability. Pharmacokinetic studies in rats showed that the bioavailability of self-made Fen capsules was 1.31 times higher than that of commercial capsules (Lipanthyl®). In summary, these results highlighted the potential of MSNs to improve the stability and oral absorption of poorly soluble drugs.

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Materials

Fenofibrate (Fen, 99 %), Cetyltrimethylammonium bromide (CTAB), Sodium salicylate (NaSal, 99 %), Tetraethyl orthosilicate (TEOS, 98 %) and Triethanolamine (TEA, for HPLC) were purchased from Aladdin Reagent Co. Ltd. Syloid® XDP 3050 (XDP 3050), Syloid® XDP3150 (XDP 3150), Syloid® 72 FP (72 FP), Syloid®244 FP (244 FP) and Syloid® AL-1 FP (AL-1 FP) were supplied from W.R. Grace & Co. Ltd. PVP K-30 was supplied from BASF SE. Fenofibric acid (99 %) was supplied from J&K Scientific.

Wanhao Qi, Jinghao Chen, Shiqiao Rui, Shi Li, Yiduo Ding, Shuaipeng Feng, Zhu Liu, Qiwei Liu, Siling Wang, Qinfu Zhao, Variable pore size of mesoporous silica in improving physical stability and oral bioavailability of insoluble drugs, International Journal of Pharmaceutics, 2025, 125394, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2025.125394.

Read also our introduction article on Mesoporous Silica here: