Nanoporous Silica Entrapped Lipid-Drug Complexes for the Solubilization and Absorption Enhancement of Poorly Soluble Drugs

This study aims to examine the contribution of nanoporous silica entrapped lipid-drug complexes (NSCs) in improving the solubility and bioavailability of dutasteride (DUT). An NSC was loaded with DUT (dissolved in lipids) and dispersed at a nanoscale level using an entrapment technique.

NSC microemulsion formation was confirmed using a ternary phase diagram, while the presence of DUT and lipid entrapment in NSC was confirmed using scanning electron microscopy. Differential scanning calorimetry and X-ray diffraction revealed the amorphous properties of NSC. The prepared all NSC had excellent flowability and enhanced DUT solubility but showed no significant difference in drug content homogeneity. An increase in the lipid content of NSC led to an increase in the DUT solubility. Further the NSC were formulated as tablets using D-α tocopheryl polyethylene glycol 1000 succinate, glyceryl caprylate/caprate, and Neusilin^®.

The NSC tablets showed a high dissolution rate of 99.6% at 30 min. Furthermore, NSC stored for 4 weeks at 60 °C was stable during dissolution testing. Pharmacokinetic studies performed in beagle dogs revealed enhanced DUT bioavailability when administered as NSC tablets. NSC can be used as a platform to develop methods to overcome the technical and commercial limitations of lipid-based preparations of poorly soluble drugs.

Materials: Dutasteride, with particle size of 1.73 μm (D50) and 4.48 μm (D90), was purchased from Dr. Reddy’s Laboratories (Hyderabad, Telangana, India). Magnesium aluminometasilicate (Mg/Al-SiO2, Neusilin® US2 (Neu)) was purchased from Fuji Chemical Industries Co., Ltd. (Gohkakizawa, Toyoma, Japan). D-Tocopheryl polyethylene glycol 1000 succinate (TPGS), glyceryl caprylate/caprate (GCC), and propylene glycol monolaurate (PGL) were obtained from Merck KGaA (Darmstadt, Germany). Croscarmellose sodium (CCS), microcrystalline cellulose (MCC), low-substituted hydroxypropyl cellulose (L-HPC), sodium stearyl fumarate (SSF), and silicified microcrystalline cellulose (SMCC) were obtained from JRS Pharma Co., Ltd. (Patterson, NY, USA); isomalt (IM) was obtained from BENEO-Palatinit GmbH (Mannheim, Germany). Hydroxypropyl methylcellulose (HPMC)- based coating agent (Opadry® 03B28796 White) was obtained from Colorcon Asia Pacific Pte Ltd. (Suwon, Korea). All other chemicals were of reagent grade and obtained commercially. All excipients for preparing the formulation were of pharmaceutical grade and obtained commercially.

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Article Information: Shin, H.-W.; Kim, J.-E.; Park, Y.-J. Nanoporous Silica Entrapped Lipid-Drug Complexes for the Solubilization and Absorption Enhancement of Poorly Soluble Drugs. Pharmaceutics 2021, 13, 63. https://doi.org/10.3390/pharmaceutics13010063