title: Effect of carbamazepine on viscoelastic properties and hot melt extrudability of Soluplus ®.
abstract: The purpose of this study was to apply viscoelastic properties of polymer and drug-polymer mixtures to determine processing conditions for the preparation of amorphous solid dispersion by melt extrusion. A poorly water-soluble drug, carbamazepine (CBZ), was mixed with Soluplus(®) as the carrier. Torque analysis using a melt extruder was performed at 10, 20 and 30% w/w drug concentrations and the effect of barrel temperature was studied. Viscosity of the mixtures either at fixed temperatures with different angular frequencies or as a function of temperature with the same frequency was studied using a rheometer. The viscosity of Soluplus(®) and the torque exerted on the twin screws decreased with the increase in CBZ concentration. The viscosity versus temperature plots for different CBZ concentrations were parallel to each other, without the drug melting transition, indicating complete drug-polymer miscibility. Thus, the drug-polymer mixtures could be extruded at temperature as low as 140°C with 10% w/w drug load, 135°C with 20% w/w drug and 125°C with 30% w/w drug, which were, respectively, ∼ 50°C, 55°C and 65°C below the melting point of 191°C for CBZ. The differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD) analyses of the binary mixtures extruded at 125-150°C showed absence of crystalline drug. A systematic study of miscibility and extrudability of drug-polymer mixtures by rheological and torque analysis as a function of temperature will help formulators select optimal melt extrusion processing conditions to develop solid dispersions.
authors.affiliation: College of Pharmacy and Health Sciences, St. John's University, 8000 Utopia Parkway, Queens, NY 11439, USA.
authors.forename: Simerdeep Singh
authors.initials: SS
authors.lastname: Gupta
authors.affiliation: College of Pharmacy and Health Sciences, St. John's University, 8000 Utopia Parkway, Queens, NY 11439, USA.
authors.forename: Tapan
authors.initials: T
authors.lastname: Parikh
authors.affiliation: College of Pharmacy and Health Sciences, St. John's University, 8000 Utopia Parkway, Queens, NY 11439, USA.
authors.forename: Anuprabha K
authors.initials: AK
authors.lastname: Meena
authors.affiliation: Catalent Pharma Solutions, 14 Schoolhouse Road, Somerset, NJ 08873, USA.
authors.forename: Nidhi
authors.initials: N
authors.lastname: Mahajan
authors.affiliation: Catalent Pharma Solutions, 14 Schoolhouse Road, Somerset, NJ 08873, USA.
authors.forename: Imre
authors.initials: I
authors.lastname: Vitez
authors.affiliation: College of Pharmacy and Health Sciences, St. John's University, 8000 Utopia Parkway, Queens, NY 11439, USA. Electronic address: serajuda@stjohns.edu.
authors.forename: Abu T M
authors.initials: ATM
authors.lastname: Serajuddin
mesh_terms: D002152:Calorimetry, Differential Scanning; D002220:Carbamazepine / Q000737:chemistry*; D004339:Drug Compounding; D004548:Elasticity; D005615:Freezing; D006358:Hot Temperature; D011092:Polyethylene Glycols / Q000737:chemistry*; D011145:Polyvinyls / Q000737:chemistry*; D033362:Powder Diffraction; D012212:Rheology; D014783:Viscosity; D014961:X-Ray Diffraction
chemical_list: D011145:Polyvinyls; C572167:polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; D002220:Carbamazepine; D011092:Polyethylene Glycols
keywords: Drug-polymer miscibility; Hot melt extrusion; Polymer; Rheology; Soluplus(®); Torque analysis; Viscosity