Improved Bioavailability and High Photostability of Methotrexate by Spray-Dried Surface-Attached Solid Dispersion with an Aqueous Medium

Low aqueous solubility and poor bioavailability are major concerns in the development of oral solid-dosage drug forms. In this study, we fabricated surface-attached solid dispersion (SASD) to enhance the solubility, bioavailability, and photostability of methotrexate (MTX), a highly lipophilic and p...

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Bibliographic Details
Published in:Pharmaceutics 2021-01, Vol.13 (1), p.111
Main Authors: Giri, Bhupendra Raj, Kim, Jung Suk, Park, Jong Hyuck, Jin, Sung Giu, Kim, Kyeong Soo, Din, Fakhar Ud, Choi, Han Gon, Kim, Dong Wuk
Format: Article
Language:English
Subjects:
Bioavailability
Drug dosages
methotrexate
Oral administration
Particle size
Permeability
photostability
Polymers
Scanning electron microscopy
solid dispersion
solubility
Solvents
Surfactants
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Summary:Low aqueous solubility and poor bioavailability are major concerns in the development of oral solid-dosage drug forms. In this study, we fabricated surface-attached solid dispersion (SASD) to enhance the solubility, bioavailability, and photostability of methotrexate (MTX), a highly lipophilic and photo-unstable drug. Several MTX-loaded SASD formulations were developed for spray-drying using water as the solvent, and were investigated for their aqueous solubility and dissolution kinetics. An optimized ternary SASD formulation composed of MTX/ sodium carboxymethyl cellulose (Na-CMC)/sodium lauryl sulfate (SLS) at 3/0.5/0.5 ( / ) had 31.78-fold and 1.88-fold higher solubility and dissolution, respectively, than MTX powder. For SASD, the in vivo pharmacokinetic parameters AUC and C were 2.90- and 3.41-fold higher, respectively, than for the MTX powder. Solid-state characterizations by differential scanning calorimetry and X-ray diffraction revealed that MTX exists in its crystalline state within the spray-dried SASD. The MTX-loaded SASD formulation showed few physical changes with photostability testing. Overall, the results indicate that the spray-dried MTX-loaded SASD formulation without organic solvents enhances the solubility and oral bioavailability of MTX without a significant deterioration of its photochemical stability.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics13010111