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Development of canagliflozin nanocrystals sublingual tablets in the presence of sodium caprate permeability enhancer: formulation optimization, characterization, in-vitro, in silico, and in-vivo study.
Fathy Elhabal, Sammar; El-Nabarawi, Mohamed A; Abdelaal, Nashwa; Elrefai, Mohamed Fathi Mohamed; Ghaffar, Shrouk A; Khalifa, Mohamed Mansour; Mohie, Passant M; Waggas, Dania S; Hamdan, Ahmed Mohsen Elsaid; Alshawwa, Samar Zuhair; Saied, Essa M; Elzohairy, Nahla A; Elnawawy, Tayseer; Gad, Rania A; Elfar, Nehal; Mohammed, Hanaa; Khasawneh, Mohammad Ahmad.
Affiliation
  • Fathy Elhabal S; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Modern University for Technology and Information (MTI), Mokattam, Cairo, Egypt.
  • El-Nabarawi MA; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
  • Abdelaal N; Department of Integrative Physiology, Baylor College of Medicine, Houston, Texas, USA.
  • Elrefai MFM; Department of Anatomy, Histology, Physiology and Biochemistry, Faculty of Medicine, The Hashemite University, Zarqa, Jordan.
  • Ghaffar SA; Department of Anatomy and Embryology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
  • Khalifa MM; Medical Affairs Department, Caduceus Lane Healthcare, Alexandria, Egypt.
  • Mohie PM; Department of Human Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt.
  • Waggas DS; Department of Human Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
  • Hamdan AME; Clinical Pharmacology, Faculty of Medicine, Alexandria, Egypt.
  • Alshawwa SZ; Department of Pathological Science, Fakeeh College for Medical Science, Jeddah, Saudi Arabia.
  • Saied EM; Department of Pharmacy Practice, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia.
  • Elzohairy NA; Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.
  • Elnawawy T; Chemistry Department, Faculty of Science, Suez Canal University, Ismailia, Egypt.
  • Gad RA; Institute for Chemistry, Humboldt Universität zu Berlin, Berlin, Germany.
  • Elfar N; Air Force Specialized Hospital, Cairo, Egypt.
  • Mohammed H; Department of Microbiology and Immunology, Faculty of Pharmacy, Modern University for Technology and Information (MTI), Mokattam, Cairo, Egypt.
  • Khasawneh MA; Department of pharmaceutics, Egyptian Drug Authority, Cairo, Egypt.
Drug Deliv ; 30(1): 2241665, 2023 Dec.
Article in En | MEDLINE | ID: mdl-37537858
Canagliflozin (CFZ) is a sodium-glucose cotransporter-2 inhibitor (SGLT2) that lowers albuminuria in type-2 diabetic patients, cardiovascular, kidney, and liver disease. CFZ is classified as class IV in the Biopharmaceutical Classification System (BCS) and is characterized by low permeability, solubility, and bioavailability, most likely attributed to hepatic first-pass metabolism. Nanocrystal-based sublingual formulations were developed in the presence of sodium caprate, as a wetting agent, and as a permeability enhancer. This formulation is suitable for children and adults and could enhance solubility, permeability, and avoid enterohepatic circulation due to absorption through the sublingual mucosa. In the present study, formulations containing various surfactants (P237, P338, PVA, and PVP K30) were prepared by the Sono-homo-assisted precipitation ion technique. The optimized formula prepared with PVP-K30 showed the smallest particle size (157 ± 0.32 nm), Zeta-potential (-18 ± 0.01), and morphology by TEM analysis. The optimized formula was subsequently formulated into a sublingual tablet containing Pharma burst-V® with a shorter disintegration time (51s) for the in-vivo study. The selected sublingual tablet improved histological and biochemical markers (blood glucose, liver, and kidney function), AMP-activated protein kinase (AMPK), and protein kinase B (AKT) pathway compared to the market formula, increased CFZ's antidiabetic potency in diabetic rabbits, boosted bioavailability by five-fold, and produced faster onset of action. These findings suggest successful treatment of diabetes with CFZ nanocrystal-sublingual tablets.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Diabetes Mellitus, Type 2 / Nanoparticles / Sodium-Glucose Transporter 2 Inhibitors Limits: Animals Language: En Journal: Drug Deliv Journal subject: FARMACOLOGIA / TERAPIA POR MEDICAMENTOS Year: 2023 Document type: Article Affiliation country: Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Diabetes Mellitus, Type 2 / Nanoparticles / Sodium-Glucose Transporter 2 Inhibitors Limits: Animals Language: En Journal: Drug Deliv Journal subject: FARMACOLOGIA / TERAPIA POR MEDICAMENTOS Year: 2023 Document type: Article Affiliation country: Country of publication: