Development and Optimization of Gastro-Retentive Controlled-Release Tablet of Calcium-Disodium Edentate and its In Vivo Gamma Scintigraphic Evaluation.
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.
['Kumar|Neeraj|N|', 'Soni|Sandeep|S|', 'Singh|Thakuri|T|', 'Kumar|Amit|A|', 'Ahmad|Farhan Jalees|FJ|', 'Bhatnagar|Aseem|A|', 'Mittal|Gaurav|G|']
D000284:Administration, Oral D000328:Adult D000818:Animals D000931:Antidotes D001682:Biological Availability D002482:Cellulose D002626:Chemistry, Pharmaceutical D019343:Citric Acid D003692:Delayed-Action Preparations D004492:Edetic Acid D005753:Gastric Mucosa D006244:Hardness D000075322:Heavy Metal Poisoning D006801:Humans D008875:Middle Aged D011041:Poisoning D011817:Rabbits D017693:Sodium Bicarbonate D012995:Solubility D013607:Tablets D055815:Young Adult
controlled-release tablet gamma scintigraphy calcium disodium EDTA heavy metal decorporation