title: Development and Optimization of Gastro-Retentive Controlled-Release Tablet of Calcium-Disodium Edentate and its In Vivo Gamma Scintigraphic Evaluation.
abstract: Medical management of heavy metal toxicity, including radioactive ones, is a cause for concern because of their increased use in energy production, healthcare, and mining. Though chelating agents like EDTA and DTPA in parenteral form are available, no suitable oral formulation is there that can trap ingested heavy metal toxicants in the stomach itself, preventing their systemic absorption. The objective of the present study was to develop and optimize gastro-retentive controlled-release tablets of calcium-disodium edentate (Ca-Na2EDTA). Gastro-retentive tablet of Ca-Na2EDTA was prepared by direct compression method. Thirteen tablet formulations were designed using HPMC-K4M, sodium chloride, and carbopol-934 along with effervescing agents sodium bicarbonate and citric acid. Tablet swelling ability, in vitro buoyancy, and drug dissolution studies were conducted in 0.1 N HCl at 37 ± 0.5°C. Ca-Na2EDTA was radiolabeled with technetium-99m for scintigraphy-based in vivo evaluation. Formula F8 (Ca-Na2EDTA 200 mg, carbopol 100 mg, avicel 55 mg, citric acid 30 mg, NaHCO3 70 mg, NaCl 100 mg, and HPMC 95 mg) was found to be optimum in terms of excellent floating properties and sustained drug release. F8 fitted best for Korsmeyer-Peppas equation with an R (2) value of 0.993. Gamma scintigraphy in humans showed mean gastric retention period of 6 h. Stability studies carried out in accordance with ICH guidelines and analyzed at time intervals of 0, 1, 2, 4, and 6 months have indicated insignificant difference in tablet hardness, drug content, total floating duration, or matrix integrity of the optimized formulation. Gastro-retentive, controlled-release tablet of Ca-Na2EDTA was successfully developed using effervescent technique as a potential oral antidote for neutralizing ingested heavy metal toxicity.
authors.affiliation: Division of Nuclear Medicine, Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organisation, Brig. SK Mazumdar Road, Delhi, 110 054, India.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Kumar
authors.affiliation: Division of Nuclear Medicine, Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organisation, Brig. SK Mazumdar Road, Delhi, 110 054, India.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Soni
authors.affiliation: Division of Nuclear Medicine, Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organisation, Brig. SK Mazumdar Road, Delhi, 110 054, India.
authors.forename: Thakuri
authors.initials: T
authors.lastname: Singh
authors.affiliation: Division of Nuclear Medicine, Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organisation, Brig. SK Mazumdar Road, Delhi, 110 054, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Jamia Hamdard, Hamdard University, Hamdard Nagar, New Delhi, 110 062, India.
authors.forename: Farhan Jalees
authors.initials: FJ
authors.lastname: Ahmad
authors.affiliation: Division of Nuclear Medicine, Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organisation, Brig. SK Mazumdar Road, Delhi, 110 054, India.
authors.forename: Aseem
authors.initials: A
authors.lastname: Bhatnagar
authors.affiliation: Division of Nuclear Medicine, Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organisation, Brig. SK Mazumdar Road, Delhi, 110 054, India. gauravmittal23@gmail.com.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Mittal
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000818:Animals; D000931:Antidotes / Q000008:administration & dosage / Q000737:chemistry; D001682:Biological Availability; D002482:Cellulose / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D019343:Citric Acid / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry*; D004492:Edetic Acid / Q000008:administration & dosage / Q000737:chemistry*; D005753:Gastric Mucosa / Q000378:metabolism*; D006244:Hardness; D000075322:Heavy Metal Poisoning; D006801:Humans; D008875:Middle Aged; D011041:Poisoning / Q000188:drug therapy; D011817:Rabbits; D017693:Sodium Bicarbonate / Q000737:chemistry; D012995:Solubility; D013607:Tablets / Q000008:administration & dosage / Q000737:chemistry*; D055815:Young Adult
chemical_list: D000931:Antidotes; D003692:Delayed-Action Preparations; D013607:Tablets; D019343:Citric Acid; D017693:Sodium Bicarbonate; D002482:Cellulose; D004492:Edetic Acid
keywords: calcium disodium EDTA; controlled-release tablet; gamma scintigraphy; heavy metal decorporation