title: Formulation optimization of hot-melt extruded abuse deterrent pellet dosage form utilizing design of experiments.
abstract: OBJECTIVE
  The objective of this study was to develop techniques for an abuse-deterrent (AD) platform utilizing the hot-melt extrusion (HME) process.
  
  
  METHODS
  Formulation optimization was accomplished by utilizing Box-Behnken design of experiments to determine the effect of the three formulation factors: PolyOx WSR301, Benecel K15M and Carbopol 71G; each of which was studied at three levels on tamper-resistant (TR) attributes of the produced melt extruded pellets. A response surface methodology was utilized to identify the optimized formulation. Lidocaine hydrochloride was used as a model drug, and suitable formulation ingredients were employed as carrier matrices and processing aids.
  
  
  RESULTS
  All of the formulations were evaluated for the TR attributes, such as particle size post-milling, gelling and percentage of drug extraction in water and alcohol. All of the design of experiments formulations demonstrated sufficient hardness and elasticity, and could not be reduced into fine particles (<150 μm), which is a desirable feature to prevent snorting. In addition, all of the formulations exhibited good gelling tendency in water with minimal extraction of drug in the aqueous medium. Moreover, Benecel K15M, in combination with PolyOx WSR301, could be utilized to produce pellets with TR potential.
  
  
  CONCLUSIONS
  HME has been demonstrated to be a viable technique with a potential to develop novel AD formulations.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, The University of Mississippi, University, MS, USA.
authors.forename: Sindhuri
authors.initials: S
authors.lastname: Maddineni
authors.forename: Sunil Kumar
authors.initials: SK
authors.lastname: Battu
authors.forename: Joe
authors.initials: J
authors.lastname: Morott
authors.forename: Majumdar
authors.initials: M
authors.lastname: Soumyajit
authors.forename: Michael A
authors.initials: MA
authors.lastname: Repka
mesh_terms: D000179:Acrylates / Q000737:chemistry; D000280:Administration, Inhalation; D002482:Cellulose / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods*; D004355:Drug Stability; D004548:Elasticity; D005079:Excipients / Q000737:chemistry*; D005615:Freezing; D005782:Gels; D006244:Hardness; D006358:Hot Temperature; D006801:Humans; D008012:Lidocaine / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D012995:Solubility; D019966:Substance-Related Disorders / Q000517:prevention & control*
chemical_list: D000179:Acrylates; D004337:Drug Carriers; D005079:Excipients; D005782:Gels; C098305:Polyox WSR-301; C492578:carbopol 71G; D011092:Polyethylene Glycols; D002482:Cellulose; D008012:Lidocaine
keywords: abuse-deterrent; design of experiment; hot-melt extrusion; insufflation; optimization