Abstract
The oral bioavailability of drugs is limited by factors such as poor membrane permeability, low solubility, and low dissolution rate. Silymarin (SLM) is a health-food active ingredient that is good for immunosuppression and tumor suppression. However, obtaining a good oral bioavailability is difficult owing to its poor solubility and low dissolution ability. To overcome these concerns, we previously prepared SLM nanoparticles (NPs) using the high-pressure crystallization method (PureNanoTM) and freeze-dried them with erythritol (Ery) or hydroxypropyl-β-CyD (HP-β-CyD) as a water-soluble dispersion stabilizer. In the present study, we investigated the mechanism underlying the improved absorption of SLM/hypromellose (HPMC)/HP-β-CyD NPs after oral administration. The SLM/HPMC nano-suspension prepared using PureNanoTM exhibited a narrow size distribution. The size of the SLM/HPMC/HP-β-CyD NPs was approximately 250 nm after hydration. The SLM/HPMC/HP-β-CyD NPs were rapidly dissolved, and demonstrated a high solubility under supersaturated conditions. Additionally, they exhibited good wettability and their membrane permeability was improved compared with that of SLM original powder. These results suggest that the formulation of SLM NPs using PureNanoTM and freeze-drying with HP-β-CyD improves the absorption of SLM after oral administration by enhancing solubility, wettability, and membrane permeability.
Highlights
Publisher’s Note: MDPI stays neutralThe oral bioavailability of a drug is limited by factors, such as membrane permeability, solubility, and dissolution rate [1,2]
In the PureNanoTM system, crystallization is immediately performed by a high shearing force, which is generated after the rapid feeding of with regard to jurisdictional claims in published maps and institutional affiliations
In this study, we investigated the relationship of the enhanced absorption of SLM to crystallization by PureNanoTM and improved its solubility by the adding HP-β-CyD
Summary
The oral bioavailability of a drug is limited by factors, such as membrane permeability, solubility, and dissolution rate [1,2]. Miniaturization of compound crystals and solid dispersions are known to improve the solubility of poorly water-soluble compounds [3,4,5,6] and is advantageous by increasing dissolution rate due to increased surface area. According to the Noyes-Whitney equation, an increase in the surface area results in fast rates of drug dissolution [7]. For poorly water-soluble drugs, such as sirolimus [8], aprepitant [9], and fenofibrate [10], micronization technology has been applied to improve the solubility of compounds. We have previously prepared nanocrystal suspensions of poorly water-soluble drugs using a continuous crystallizer (PureNanoTM ) [14]. In the PureNanoTM system, crystallization is immediately performed by a high shearing force, which is generated after the rapid feeding of with regard to jurisdictional claims in published maps and institutional affiliations
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