title: Amorphous-state characterization of efavirenz--polymer hot-melt extrusion systems for dissolution enhancement.
abstract: The aim of this study was to improve the dissolution rate of efavirenz (EFV) by formulating a physically stable dispersion in polymers. Hot-melt extrusion (HME) was used to prepare solid solutions of EFV with Eudragit EPO (a low-glass transition polymer) or Plasdone S-630 (a high-glass transition polymer). The drug-polymer blends were characterized for their thermal and rheological properties as a function of drug concentration to understand their miscibility and processability by HME. The solid-state stability of extrudates was characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, and dissolution studies. Thermal and rheological studies revealed that the drug is miscible with both polymers, and a decrease in melt viscosity was observed as the drug concentration increased. XRD and DSC studies confirmed the existence of amorphous state of EFV in the extrudates during storage. The dissolution rate of EFV from the extrudates was substantially higher than the crystalline drug. FTIR studies revealed an interaction between the EFV and Plasdone S-630, which reduced the molecular mobility and prevented crystallization upon storage. EFV and Eudragit EPO systems lack specific interactions, but are less susceptible to crystallization due to the antiplasticization effect of the polymer.
authors.affiliation: Department of Pharmacal Sciences, Auburn University, Auburn, Alabama 36849, USA.
authors.forename: Sateesh Kumar
authors.initials: SK
authors.lastname: Sathigari
authors.forename: Vinod K
authors.initials: VK
authors.lastname: Radhakrishnan
authors.forename: Virginia A
authors.initials: VA
authors.lastname: Davis
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Parsons
authors.forename: R Jayachandra
authors.initials: RJ
authors.lastname: Babu
mesh_terms: D000480:Alkynes; D019380:Anti-HIV Agents / Q000737:chemistry*; D048588:Benzoxazines / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D018360:Crystallography, X-Ray; D003521:Cyclopropanes; D004337:Drug Carriers; D004355:Drug Stability; D004356:Drug Storage; D006358:Hot Temperature; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008956:Models, Chemical; D011109:Polymethacrylic Acids / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry*; D012212:Rheology; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013678:Technology, Pharmaceutical / Q000379:methods*; D044366:Transition Temperature; D014783:Viscosity
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D004337:Drug Carriers; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; D011205:Povidone; C098320:efavirenz