title: Reutilization of Tacrolimus Extracted from Expired Prograf® Capsules: Physical, Chemical, and Pharmacological Assessment.
abstract: In this study, we investigated whether tacrolimus extracted and purified from the commercial capsules (Prograf® 5 mg) have retained its original quality and activity beyond the capsules expiration date in order to be reused for research purposes after extraction. High-performance liquid chromatography (HPLC) assay method was developed and validated for the quantification of tacrolimus, using cyclosporine A as an internal standard (IS). Moreover, a combination of analytical methods, including nuclear magnetic resonance (NMR), gas chromatography-mass spectrometry (GC-MS), Fourier transform-infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), and differential scanning calorimetry (DSC) were used to assess the quality of extracted/purified tacrolimus. Suppression of murine peripheral-blood mononuclear cells (PBMC) proliferation and the levels of interleukin-2 (IL-2) and interferon gamma (IFN-γ) were also assessed. The data obtained showed no detectable differences in the quality profile between the authentic sample and extracted drug. Also, the results showed that the extracted/purified tacrolimus was able to suppress T cell proliferation, induced by concanavalin A, indicating the retained pharmacological activity. We proved that tacrolimus extracted/purified from expired Prograf® capsuled retains its purity and immunosuppressive activity and can be reused for research and possibly in pharmaceutical manufacturing.
authors.affiliation: Nanomedicine Research Unit, Department of Pharmaceutics, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia.|King Abdullah Institute for Nanotechnology, King Saud University, Riyadh, Saudi Arabia.|King Salman Bin Abdulaziz Chair for Kidney Disease, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Ziyad
authors.initials: Z
authors.lastname: Binkhathlan
authors.affiliation: Nanomedicine Research Unit, Department of Pharmaceutics, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia.
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Badran
authors.affiliation: Nanomedicine Research Unit, Department of Pharmaceutics, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Alomrani
authors.affiliation: Nanomedicine Research Unit, Department of Pharmaceutics, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia.
authors.forename: Ibrahim A
authors.initials: IA
authors.lastname: Aljuffali
authors.affiliation: King Salman Bin Abdulaziz Chair for Kidney Disease, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Alghonaim
authors.affiliation: Prince Naif Center for Immunology Research, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Saleh
authors.initials: S
authors.lastname: Al-Muhsen
authors.affiliation: Prince Naif Center for Immunology Research, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Rabih
authors.initials: R
authors.lastname: Halwani
authors.affiliation: Nanomedicine Research Unit, Department of Pharmaceutics, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia. aalshamsan@ksu.edu.sa.|King Abdullah Institute for Nanotechnology, King Saud University, Riyadh, Saudi Arabia. aalshamsan@ksu.edu.sa.|King Salman Bin Abdulaziz Chair for Kidney Disease, King Saud University, Riyadh, Saudi Arabia. aalshamsan@ksu.edu.sa.
authors.forename: Aws
authors.initials: A
authors.lastname: Alshamsan
mesh_terms: D000818:Animals; D002214:Capsules / Q000737:chemistry* / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D016572:Cyclosporine / Q000737:chemistry; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D051379:Mice; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D016559:Tacrolimus / Q000737:chemistry* / Q000494:pharmacology*; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D002214:Capsules; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D007371:Interferon-gamma; D016572:Cyclosporine; D016559:Tacrolimus
keywords: extraction; immunosuppression; purity; tacrolimus; validation