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

Abstract

settings Open AccessArticle Improved Bioavailability and High Photostability of Methotrexate by Spray-Dried Surface-Attached Solid Dispersion with an Aqueous Medium by Bhupendra Raj Giri 1,†OrcID,Jung Suk Kim 2,†OrcID,Jong Hyuck Park 2,Sung Giu Jin 3OrcID,Kyeong Soo Kim 4,Fakhar ud Din 5OrcID,Han Gon Choi 2,*OrcID andDong Wuk Kim 1,*OrcID 1 College of Pharmacy, Research Institute of Pharmaceutical Sciences, Vessel-Organ Interaction Research Center (VOICE, MRC), BK21 FOUR Community-Based Intelligent Novel Drug Discovery Education Unit, Kyungpook National University, Daegu 41566, Korea 2 College of Pharmacy, Hanyang University, Ansan 15588, Korea 3 Department of Pharmaceutical Engineering, Dankook University, Cheonan 31116, Korea 4 Department of Pharmaceutical Engineering, Gyeongnam National University of Science and Technology, Jinju 52725, Korea 5 Department of Pharmacy, Quaid-I-Azam University, Islamabad 45320, Pakistan * Authors to whom correspondence should be addressed. † These authors contributed equally to this work. Pharmaceutics 2021, 13(1), 111; https://doi.org/10.3390/pharmaceutics13010111 Received: 31 December 2020 / Revised: 12 January 2021 / Accepted: 14 January 2021 / Published: 16 January 2021 (This article belongs to the Special Issue Novel Strategies for Enhancing Oral Bioavailability and/or Biopharmaceutics-Related Research) Download PDF Browse Figures Citation Export Abstract 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 (w/w) 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 Cmax 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.