Physicochemical Properties of Solid Phospholipid Particles as a Drug Delivery Platform for Improving Oral Absorption of Poorly Soluble Drugs
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Abstract
Purpose
A novel drug delivery platform, mesoporous phospholipid particle (MPP), is introduced. Its physicochemical properties and ability as a carrier for enhancing oral absorption of poorly soluble drugs are discussed.
Methods
MPP was prepared through freeze-drying a cyclohexane/t-butyl alcohol solution of phosphatidylcholine. Its basic properties were revealed using scanning electron microscopy, x-ray diffraction, thermal analysis, hygroscopicity measurement, and so on. Fenofibrate was loaded to MPP as a poorly soluble model drug, and effect of MPP on the oral absorption behavior was observed.
Results
MPP is spherical in shape with a diameter typically in the range of 10–15 μm and a wide surface area that exceeds 10 m2/g. It has a bilayer structure that may accommodate hydrophobic drugs in the acyl chain region. When fenofibrate was loaded in MPP as a model drug, it existed partially in a crystalline state and improvement in the dissolution behavior was achieved in the presence of a surfactant, because of the formation of mixed micelles composed of phospholipids and surfactants in the dissolution media. MPP greatly improved the oral absorption of fenofibrate compared to that of the crystalline drug and its efficacy was almost equivalent to that of an amorphous drug dispersion.
Conclusion
MPP is a promising option for improving the oral absorption of poorly soluble drugs based on the novel mechanism of dissolution improvement.
KEY WORDS
oral absorption phospholipid poorly soluble drugABBREVIATIONS
- BuOH
Buthyl alcohol
- DSC
Differential scanning calorimetry
- DTA
Differential thermal analysis
- FEN
Fenofibrate
- FIB
Focused ion beam
- HSPC
Hydrogenated soybean phosphatidylcholine
- MPP
Mesoporous phospholipid particle
- SD
Solid dispersion
- SEM
Scanning electron microscopy
- TCNa
Sodium taurocholate
- TGA
Thermogravimetric analysis
- XRPD
X-ray powder diffraction
Notes
ACKNOWLEDGMENTS AND DISCLOSURES
The authors wish to thank Dr. Kaoru Murata (FEI Company) for performing the FIB-milling SEM investigation. Mr. Yasushiro Otsuka (TA Instruments Japan) is also acknowledged for the hygroscopicity measurement. This work was in part supported by Hosokawa Powder Technology Foundation and World Premier International Research Center (WPI) Initiative on Materials Nanoarchitectonics, MEXT, Japan.
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