title: Investigation of the interactions of enteric and hydrophilic polymers to enhance dissolution of griseofulvin following hot melt extrusion processing.
abstract: OBJECTIVE
  This study focuses on the application of hot melt extrusion (HME) to produce solid dispersions containing griseofulvin (GF) and investigates the in-vitro dissolution performance of HME powders and resulting tablet compositions containing HME-processed dispersions.
  
  
  METHODS
  Binary, ternary and quaternary dispersions containing GF, enteric polymer (Eudragit L100-55 or AQOAT-LF) and/or vinyl pyrrolidone-based polymer (Plasdone K-12 povidone or S-630 copovidone) were processed by HME. Two plasticizers, triethyl citrate (TEC) and acetyl tributyl citrate (ATBC), were incorporated to aid in melt processing and to modify release of GF in neutral media following a pH-change in dissolution. Products were characterized for GF recovery, degrees of compositional amorphous character, intermolecular interactions and non-sink dissolution performance.
  
  
  RESULTS
  Binary dispersions exhibited lower maximum observed concentration values and magnitudes of supersaturated GF in neutral media dissolution in comparison with the ternary dispersions. The quaternary HME products, 1 : 2 : 1 : 0.6 GF : L100-55 : S-630 : ATBC and GF : AQOAT-LF : K-12 : ATBC, were determined as the most optimal concentration-enhancing compositions due to increased hydrogen bonding of enteric functional groups with carbonyl/acetate groups of vinyl pyrrolidone-based polymers, reduced compositional crystallinity and presence of incorporated hydrophobic plasticizer.
  
  
  CONCLUSIONS
  HME products containing combinations of concentration-enhancing polymers can supersaturate and sustain GF dissolution to greater magnitudes in neutral media following the pH-transition and be compressed into immediate-release tablets exhibiting similar dissolution profiles.
authors: Division of Pharmaceutics, The University of Texas at Austin, Austin, TX, USA.
authors: Ryan C
authors: RC
authors: Bennett
authors: Division of Pharmaceutics, The University of Texas at Austin, Austin, TX, USA.
authors: Justin M
authors: JM
authors: Keen
authors: Pharmaceutical and Nutritional Technology, R&D, Ashland Specialty Ingredients, Wilmington, DE, USA.
authors: Yunxia Vivian
authors: YV
authors: Bi
authors: Pharmaceutical and Nutritional Technology, R&D, Ashland Specialty Ingredients, Wilmington, DE, USA.
authors: Stuart
authors: S
authors: Porter
authors: Pharmaceutical and Nutritional Technology, R&D, Ashland Specialty Ingredients, Wilmington, DE, USA.
authors: Thomas
authors: T
authors: Dürig
authors: Division of Pharmaceutics, The University of Texas at Austin, Austin, TX, USA.
authors: James W
authors: JW
authors: McGinity
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D002951:Citrates / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods; D006118:Griseofulvin / Q000737:chemistry*; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D010968:Plasticizers / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry; D011208:Powders / Q000737:chemistry; D012995:Solubility; D013607:Tablets / Q000737:chemistry
chemical_list: D000180:Acrylic Resins; D002951:Citrates; D004337:Drug Carriers; C446821:Eudragit L100-55; D010968:Plasticizers; D011108:Polymers; D011208:Powders; D013607:Tablets; C014953:2-acetyltributylcitrate; D006118:Griseofulvin; C023001:ethyl citrate; D011205:Povidone
keywords: amorphous solid dispersions; copovidone; plasticizer; poorly water-soluble compound; povidone