title: Formulation and development of pH-independent/dependent sustained release matrix tablets of ondansetron HCl by a continuous twin-screw melt granulation process.
abstract: The objective of the present study was to develop pH-independent/dependent sustained release (SR) tablets of ondansetron HCl dihydrate (OND), a selective 5-HT3 receptor antagonist that is used for prevention of nausea and vomiting caused by chemotherapy, radiotherapy and postoperative treatment. The challenge with the OND API is its pH-dependent solubility and relatively short elimination half-life. Therefore, investigations were made to solve these problems in the current study. Formulations were prepared using stearic acid as a binding agent via a melt granulation process in a twin-screw extruder. The micro-environmental pH of the tablet was manipulated by the addition of fumaric acid to enhance the solubility and release of OND from the tablet. The in vitro release study demonstrated sustained release for 24h with 90% of drug release in formulations using stearic acid in combination with ethyl cellulose, whereas 100% drug release in 8h for stearic acid-hydroxypropylcellulose matrices. The formulation release kinetics was correlated to the Higuchi diffusion model and a non-Fickian drug release mechanism. The results of the present study demonstrated for the first time the pH dependent release from hydrophilic-lipid matrices as well as pH independent release from hydrophobic-lipid matrices for OND SR tablets manufactured by means of a continuous melt granulation technique utilizing a twin-screw extruder.
authors: Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USA.
authors: Hemlata
authors: H
authors: Patil
authors: Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USA.
authors: Roshan V
authors: RV
authors: Tiwari
authors: Catalent Pharma Solutions, 14 School House Road, Somerset, NJ 08873, USA.
authors: Sampada B
authors: SB
authors: Upadhye
authors: Catalent Pharma Solutions, 14 School House Road, Somerset, NJ 08873, USA.
authors: Ronald S
authors: RS
authors: Vladyka
authors: Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USA; Center for Pharmaceutical Technology, School of Pharmacy, The University of Mississippi, Oxford, MS 38677, USA. Electronic address: marepka@olemiss.edu.
authors: Michael A
authors: MA
authors: Repka
mesh_terms: D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003692:Delayed-Action Preparations; D004339:Drug Compounding / Q000379:methods*; D065546:Drug Liberation; D005079:Excipients / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D017294:Ondansetron / Q000008:administration & dosage* / Q000737:chemistry; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000737:chemistry; D012995:Solubility; D013229:Stearic Acids / Q000737:chemistry; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D003692:Delayed-Action Preparations; D005079:Excipients; D012702:Serotonin Antagonists; D013229:Stearic Acids; D013607:Tablets; D017294:Ondansetron; C031183:stearic acid; C013517:ethyl cellulose; D002482:Cellulose; C008079:hydroxypropylcellulose
keywords: Hot melt extrusion; Melt-granulation; Ondansetron; Sustain release; pH-dependent/independent drug release