title: Optimization of hot melt extrusion parameters for sphericity and hardness of polymeric face-cut pellets.
abstract: The aim of this study was to formulate face-cut, melt-extruded pellets, and to optimize hot melt process parameters to obtain maximized sphericity and hardness by utilizing Soluplus(®) as a polymeric carrier and carbamazepine (CBZ) as a model drug. Thermal gravimetric analysis (TGA) was used to detect thermal stability of CBZ. The Box-Behnken design for response surface methodology was developed using three factors, processing temperature ( °C), feeding rate (%), and screw speed (rpm), which resulted in 17 experimental runs. The influence of these factors on pellet sphericity and mechanical characteristics was assessed and evaluated for each experimental run. Pellets with optimal sphericity and mechanical properties were chosen for further characterization. This included differential scanning calorimetry, drug release, hardness friability index (HFI), flowability, bulk density, tapped density, Carr's index, and fourier transform infrared radiation (FTIR) spectroscopy. TGA data showed no drug degradation upon heating to 190 °C. Hot melt extrusion processing conditions were found to have a significant effect on the pellet shape and hardness profile. Pellets with maximum sphericity and hardness exhibited no crystalline peak after extrusion. The rate of drug release was affected mainly by pellet size, where smaller pellets released the drug faster. All optimized formulations were found to be of superior hardness and not friable. The flow properties of optimized pellets were excellent with high bulk and tapped density.
authors.affiliation: a Department of Pharmaceutics and Drug Delivery, School of Pharmacy , The University of Mississippi, University , MS , USA ;|b Department of Pharmaceutics, College of Pharmacy , Prince Sattam Bin Abdulaziz University , Alkharj , Saudi Arabia ;
authors.forename: Abdullah S
authors.initials: AS
authors.lastname: Alshetaili
authors.affiliation: a Department of Pharmaceutics and Drug Delivery, School of Pharmacy , The University of Mississippi, University , MS , USA ;
authors.forename: Bjad K
authors.initials: BK
authors.lastname: Almutairy
authors.affiliation: b Department of Pharmaceutics, College of Pharmacy , Prince Sattam Bin Abdulaziz University , Alkharj , Saudi Arabia ;
authors.forename: Saad M
authors.initials: SM
authors.lastname: Alshahrani
authors.affiliation: a Department of Pharmaceutics and Drug Delivery, School of Pharmacy , The University of Mississippi, University , MS , USA ;
authors.forename: Eman A
authors.initials: EA
authors.lastname: Ashour
authors.affiliation: a Department of Pharmaceutics and Drug Delivery, School of Pharmacy , The University of Mississippi, University , MS , USA ;
authors.forename: Roshan V
authors.initials: RV
authors.lastname: Tiwari
authors.affiliation: c Department of Pharmaceutics, College of Pharmacy , King Saud University , Riyadh , Saudi Arabia ;
authors.forename: Sultan M
authors.initials: SM
authors.lastname: Alshehri
authors.affiliation: a Department of Pharmaceutics and Drug Delivery, School of Pharmacy , The University of Mississippi, University , MS , USA ;
authors.forename: Xin
authors.initials: X
authors.lastname: Feng
authors.affiliation: b Department of Pharmaceutics, College of Pharmacy , Prince Sattam Bin Abdulaziz University , Alkharj , Saudi Arabia ;
authors.forename: Bader B
authors.initials: BB
authors.lastname: Alsulays
authors.affiliation: a Department of Pharmaceutics and Drug Delivery, School of Pharmacy , The University of Mississippi, University , MS , USA ;
authors.forename: Soumyajit
authors.initials: S
authors.lastname: Majumdar
authors.affiliation: d BASF Corporation , Tarrytown , NY , USA ;
authors.forename: Nigel
authors.initials: N
authors.lastname: Langley
authors.affiliation: e R&D Project, Management Excipients, BASF SE , Ludwigshafen , Germany ;
authors.forename: Karl
authors.initials: K
authors.lastname: Kolter
authors.affiliation: f Global Development and Technical Marketing, BASF SE , Ludwigshafen , Germany ;
authors.forename: Andreas
authors.initials: A
authors.lastname: Gryczke
authors.affiliation: g Thermo Fisher Scientific , Tewksbury , MA , USA ;
authors.forename: Scott T
authors.initials: ST
authors.lastname: Martin
authors.affiliation: a Department of Pharmaceutics and Drug Delivery, School of Pharmacy , The University of Mississippi, University , MS , USA ;|h Pii Center for Pharmaceutical Technology, The University of Mississippi, University , MS , USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Repka
mesh_terms: D002220:Carbamazepine / Q000737:chemistry*; D065546:Drug Liberation / Q000187:drug effects*; D004355:Drug Stability; D006358:Hot Temperature; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011145:Polyvinyls / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D011108:Polymers; D011145:Polyvinyls; D002220:Carbamazepine; D011092:Polyethylene Glycols
keywords: Box–Behnken design; Soluplus®; carbamazepine; design of experiment; face-cut pellets; hardness; hot melt extrusion; sphericity