Properties of enteric coated sodium valproate pellets.
The influence of subcoat application and micro-environmental pH on the dissolution properties of enteric coated sodium valproate pellets was investigated. The pellets were prepared by solution-layering or wet-mass extrusion-spheronization methods. In order to pass the USP enteric test, the solution-layered and wet-mass extruded pellets required 35 and 25% weight gain of Eudragit L 30D-55, respectively. The application of a subcoat of either Methocel-E5 (HPMC) or Opadry AMB to the pellets resulted in a delay in sodium valproate release in 0.1N HCl. Further delay in drug release was observed when citric acid was present in a HPMC subcoat or when added to the core pellet formulation. The amount of drug released from coated pellets was a function of the level of citric acid in the pellet core or subcoat and subsequent micro-environmental pH of the pellets. Citric acid exerted a plasticizing effect on the enteric polymer film and improved film formation and polymer coalescence. When greater than 10% (w/w) citric acid was present in the pellets, a decrease in drug content was observed due to the conversion of sodium valproate to the volatile compound, valproic acid. Pellets containing less than 10% (w/w) citric acid maintained potency during processing.
Bruce
L Diane
LD
Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA. diane.bruce@quintiles.com
Petereit
Hans-Ulrich
HU
Beckert
Thomas
T
McGinity
James W
JW
D000927:Anticonvulsants / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D019343:Citric Acid / Q000737:chemistry; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D013058:Mass Spectrometry; D008689:Methacrylates / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D011108:Polymers / Q000737:chemistry; D012995:Solubility; D013608:Tablets, Enteric-Coated; D013818:Thermogravimetry; D013997:Time Factors; D014635:Valproic Acid / Q000737:chemistry*; D014867:Water / Q000737:chemistry
D000927:Anticonvulsants; C477852:Eudragit L 30 D-55; D005079:Excipients; D008689:Methacrylates; D011108:Polymers; D013608:Tablets, Enteric-Coated; D014867:Water; D019343:Citric Acid; D014635:Valproic Acid