Development of 20(S)-Protopanaxadiol-Loaded SNEDDS Preconcentrate Using Comprehensive Phase Diagram for the Enhanced Dissolution and Oral Bioavailability

Young Hoon Kim,Kyoung Ah Min,Kwan Hyung Cho,Jenisha Karmacharya,Han-Joo Maeng,Dong-Jin Jang,Thi-Thao-Linh Nguyen,Yu Chul Kim

doi:10.3390/pharmaceutics12040362

Young Hoon Kim, Kyoung Ah Min + Show 6 more

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https://doi.org/10.3390/pharmaceutics12040362

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Journal: Pharmaceutics	Publication Date: Apr 15, 2020
Citations: 9	License type: CC BY 4.0

Affiliation: Inje University, Gachon University

Abstract

In this study, we aimed to develop a 20(S)-protopanaxadiol (PPD)-loaded self-nanoemulsifying drug delivery system (SNEDDS) preconcentrate (PSP) using comprehensive ternary phase diagrams for enhanced solubility, physical stability, dissolution, and bioavailability. Capmul MCM C8 and Capryol 90 were selected as the oil phase owing to the high solubility of PPD in these vehicles (>15%, w/w). Novel comprehensive ternary phase diagrams composed of selected oil, surfactant, and PPD were constructed, and the solubility of PPD and particle size of vehicle was indicated on them for the effective determination of PSP. PSPs were confirmed via particle size distribution, physical stability, and scanning electron microscope (SEM) with the dispersion of water. The optimized PSP (CAPRYOL90/Kolliphor EL/PPD = 54/36/10, weight%) obtained from the six possible comprehensive ternary phase diagrams showed a uniform nanoemulsion with the particle size of 125.07 ± 12.56 nm without any PPD precipitation. The PSP showed a dissolution rate of 94.69 ± 2.51% in 60 min at pH 1.2, whereas raw PPD showed negligible dissolution. In oral pharmacokinetic studies, the PSP group showed significantly higher Cmax and AUCinf values (by 1.94- and 1.81-fold, respectively) than the raw PPD group (p < 0.05). In conclusion, the PSP formulation with outstanding solubilization, dissolution, and in-vivo oral bioavailability could be suggested using effective and comprehensive ternary phase diagrams.

Highlights

To improve the dissolution and in-vivo oral bioavailability of PPD, researchers have utilized several formulation technologies, such as nanosuspension formulations prepared by anti-solvent precipitation methods or solid dispersions by melting solvent methods [12,14]
The present study suggested that the formulations of PPD-loaded self-nanoemulsifying drug delivery system (SNEDDS) preconcentrate (PSP) may be efficiently optimized by a novel comprehensive phase diagram method based on physicochemical examination
To determine the oil and surfactant components suitable for solubilizing PPD in the PSP, PPD solubility was evaluated in various types of oils and surfactants (Figure 2)

Summary

Introduction

To improve the dissolution and in-vivo oral bioavailability of PPD, researchers have utilized several formulation technologies, such as nanosuspension formulations prepared by anti-solvent precipitation methods or solid dispersions by melting solvent methods [12,14]. The present study suggested that the formulations of PPD-loaded SNEDDS preconcentrate (PSP) may be efficiently optimized by a novel comprehensive phase diagram method based on physicochemical examination. The regions in the phase diagram present the factors determining the formation of SNEDDS preconcentrates (i.e., vehicle dispersibility, drug loading content (%), and drug solubility). The construction of comprehensive phase diagrams suggested in this study could be a promising strategy for developing oral formulations containing drug molecules with the challenging characteristics of low solubility and poor oral bioavailability

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