title: Evaluation of the drug solubility and rush ageing on drug release performance of various model drugs from the modified release polyethylene oxide matrix tablets.
abstract: Hydrophilic matrix systems are currently some of the most widely used drug delivery systems for controlled-release oral dosage forms. Amongst a variety of polymers, polyethylene oxide (PEO) is considered an important material used in pharmaceutical formulations. As PEO is sensitive to thermal oxidation, it is susceptible to free radical oxidative attack. The aim of this study was to investigate the stability of PEO based formulations containing different model drugs with different water solubility, namely propranolol HCl, theophylline and zonisamide. Both polyox matrices 750 and 303 grade were used as model carriers for the manufacture of tablets stored at 40 °C. The results of the present study suggest that the drug release from the matrix was affected by the length of storage conditions, solubility of drugs and the molecular weight of the polymers. Generally, increased drug release rates were prevalent in soluble drug formulations (propranolol) when stored at the elevated temperature (40 °C). In contrast, it was not observed with semi soluble (theophylline) and poorly soluble (zonisamide) drugs especially when formulated with PEO 303 polymer. This indicates that the main parameters controlling the drug release from fresh polyox matrices are the solubility of the drug in the dissolution medium and the molecular weight of the polymer. DSC traces indicated that that there was a big difference in the enthalpy and melting points of fresh and aged PEO samples containing propranolol, whereas the melting point of the aged polyox samples containing theophylline and zonisamide was unaffected. Graphical abstract ᅟ.
authors.affiliation: Medway School of Pharmacy, University of Kent, Chatham Maritime, Chatham, ME4 4TB, UK.|Hamadan University of Medical Science, Daneshgah-e-Bu Ali Sina, Hamadan, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Shojaee
authors.affiliation: Department of Pharmacy/Chemistry, School of Life Sciences, University of Sussex, Falmer, Brighton, BN1 9QJ, UK. A.Nokhodchi@sussex.ac.uk.|Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. A.Nokhodchi@sussex.ac.uk.
authors.forename: Ali
authors.initials: A
authors.lastname: Nokhodchi
authors.affiliation: Hamadan University of Medical Science, Daneshgah-e-Bu Ali Sina, Hamadan, Iran. M.Maniruzzaman@sussex.ac.uk.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Maniruzzaman
mesh_terms: D003692:Delayed-Action Preparations / Q000737:chemistry; D065546:Drug Liberation; D004355:Drug Stability; D006244:Hardness; D007555:Isoxazoles / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D011433:Propranolol / Q000737:chemistry; D012995:Solubility; D013607:Tablets; D013806:Theophylline / Q000737:chemistry; D000078305:Zonisamide
chemical_list: D003692:Delayed-Action Preparations; D007555:Isoxazoles; D013607:Tablets; D011092:Polyethylene Glycols; D000078305:Zonisamide; D011433:Propranolol; D013806:Theophylline
keywords: Controlled release; Drug release; Drug solubility; Polyox matrices; Stability