International Journal of Pharmaceutics 367 (2009) 20–28 Contents lists available at ScienceDirect International Journal of Pharmaceutics journal homepage: www.elsevier.com/locate/ijpharm Influence of polymeric subcoats on the drug release properties of tablets powder-coated with pre-plasticized Eudragit ® L 100-55 Dorothea Sauer a,∗ , Alan B. Watts a , Lonique B. Coots a , Weijia C. Zheng b , James W. McGinity a a Drug Dynamics Institute, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, United States b Novartis Institutes for BioMedical Research Inc., Chemical and Pharmaceutical Profiling, 250 Massachusetts Avenue, Cambridge, MA 02139, United States article info Article history: Received 2 May 2008 Received in revised form 8 September 2008 Accepted 9 September 2008 Available online 20 September 2008 Keywords: Dry powder coating Sodium valproate Enteric Eudragit Subcoat Pore forming agent abstract The aim of the study was to investigate the properties of sodium valproate tablets that were dry powder- coated with pre-plasticized Eudragit ® L 100-55. Polyethylene glycol 3350 (PEG 3350) was used as primer to facilitate initial coating powder adhesion. Solubility parameters were employed to determine the wetting properties of the PEG 3350 primer. Additional PEG 3350 within the powder coating formulation was required to enable powder adhesion to the tablet cores. The application of a subcoat of either Eudragit ® E PO or Eudragit ® RL PO facilitated adhesion of the enteric polymer to the tablet cores and reduced the amount PEG 3350 required in the coating formulation. Since reduction of the PEG 3350 content produced less water-vapor permeable films, the enteric coating level necessary to control the drug release was decreased. PEG 3350 and Methocel ® K4M were incorporated in both Eudragit ® E PO and Eudragit ® RL PO subcoating formulations as pore forming agents. The influence of the pore forming excipients on physicochemical properties of free powder-cast films was investigated. The miscibility of the PEG 3350 and Methocel ® K4M in the film coating was correlated with their ability to function as pore forming agent. © 2008 Elsevier B.V. All rights reserved. 1. Introduction Dry powder coating of pharmaceutical dosage forms was first investigated by Obara et al. in the late 1990s (Obara et al., 1999). The process was later modified by Kablitz et al. (2006) and Pearnchob and Bodmeier (2003). Recently, a new liquid free coating technique for tablets was developed by Cerea et al. and Zheng et al. using the acrylic polymers Eudragit ® E PO and mixtures of Eudragit ® RL PO and RS PO (Cerea et al., 2004; Zheng et al., 2004). The process did not require the use of organic solvents or water. Powder coating is a suitable technique for water-sensitive drugs and can reduce interactions between the API and functional polymers in aqueous coating applications. Powder coating has been shown to signifi- cantly reduce processing times (Pearnchob and Bodmeier, 2003), prevent aging of polymer films (Zheng et al., 2004), and reduce the migration of drugs into functional coatings (Sauer et al., 2007). Sodium valproate is a very water-soluble, heat-stable, deliques- cent salt with a pKa of 4.8 (Chang, 1979). It has been reported that sodium valproate tablets and pellets required high coating levels of an enteric polymer, even with the application of either a Methocel ® E5 or Opadry ® AMB subcoat (Bruce et al., 2003b). Several mech- ∗ Corresponding author. Tel.: +1 512 232 4088; fax: +1 512 471 7474. E-mail address: sauer@mail.utexas.edu (D. Sauer). anisms have been proposed in the literature to explain why cores containing highly soluble model drugs require high coating levels of a functional polymer to control the drug release. In aqueous coating operations, highly water-soluble active pharmaceutical ingredients (APIs) can dissolve and partition into the film coating, which may compromise film integrity during dissolution (Ghebre-Sellassie et al., 1987). In this case, an elevated polymer weight gain is required to control the drug release. Other researchers have found that high levels of an enteric polymer are necessary to delay drug release of an alkaline API in acidic media (Dangel et al., 2000; Deasy and O’Connell, 1984). The presence of a weak base in the core formu- lation of an enteric-coated dosage form was shown to cause high absorption of simulated gastric fluid and premature drug release at low coating levels (Dangel et al., 2000). Dissociation of the salts at the interface between enteric coating and core due to water penetration through the enteric coating may affect the microen- vironmental pH. As a result, active pharmaceutical ingredients or excipients based of a weak acid and a strong base may decrease the stability of the enteric coating in gastric fluid and subcoatings were recommended to prevent this phenomenon (Dittgen et al., 1997). Subcoating materials have been widely used in combination with enteric polymers to promote adhesion of the functional poly- mer (Obara et al., 1999), function as a moisture barrier (Felton et al., 1995), and prevent interactions between an API and enteric coat- ing (Bozdag et al., 1999). Other researchers described an increased gastric resistance of enteric-coated dosage forms in the presence 0378-5173/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.ijpharm.2008.09.020