Assessing Mixing Quality of a Copovidone-TPGS Hot Melt Extrusion Process with Atomic Force Microscopy and Differential Scanning Calorimetry.
Atomic force microscopy (AFM) and modulated differential scanning calorimetry (mDSC) were used to evaluate the extent of mixing of a hot melt extrusion process for producing solid dispersions of copovidone and D-α-tocopherol polyethylene glycol 1000 succinate (TPGS 1000). In addition to composition, extrusion process parameters of screw speed and thermal quench rate were varied. The data indicated that for 10% TPGS and 300 rpm screw speed, the mixing was insufficient to yield a single-phase amorphous material. AFM images of the extrudate cross section for air-cooled material indicate round domains 200 to 700 nm in diameter without any observed alignment resulting from the extrusion whereas domains in extrudate subjected to chilled rolls were elliptical in shape with uniform orientation. Thermal analysis indicated that the domains were predominantly semi-crystalline TPGS. For 10% TPGS and 600 rpm screw speed, AFM and mDSC data were consistent with that of a single-phase amorphous material for both thermal quench rates examined. When the TPGS concentration was reduced to 5%, a single-phase amorphous material was achieved for all conditions even the slowest screw speed studied (150 rpm).
Formulation Sciences Department, Merck Research Laboratories, Merck and Co., Inc., Rahway, New Jersey, USA. matthew.lamm@merck.com.|Merck Research Laboratories, RY-80T-A128, 126 East Lincoln Avenue, Rahway, New Jersey, 07065, USA. matthew.lamm@merck.com.
Matthew S
MS
Lamm
Formulation Sciences Department, Merck Research Laboratories, Merck and Co., Inc., Kenilworth, New Jersey, USA.
James
J
DiNunzio
Formulation Sciences Department, Merck Research Laboratories, Merck and Co., Inc., Rahway, New Jersey, USA.
Nazia N
NN
Khawaja
Formulation Sciences Department, Merck Research Laboratories, Merck and Co., Inc., Rahway, New Jersey, USA.
Louis S
LS
Crocker
Formulation Sciences Department, Merck Research Laboratories, Merck and Co., Inc., Kenilworth, New Jersey, USA.
Anthony
A
Pecora
D002152:Calorimetry, Differential Scanning / Q000379:methods*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods*; D006358:Hot Temperature; D018625:Microscopy, Atomic Force / Q000379:methods*; D011108:Polymers / Q000737:chemistry; D011759:Pyrrolidines / Q000737:chemistry*; D014753:Vinyl Compounds / Q000737:chemistry*; D014810:Vitamin E / Q000737:chemistry*
D004337:Drug Carriers; D011108:Polymers; D011759:Pyrrolidines; D014753:Vinyl Compounds; C402301:poly(vinylpyrrolidone-co-vinyl-acetate); D014810:Vitamin E; C014225:tocophersolan
TPGS 1000; atomic force microscopy (AFM); copovidone; differential scanning calorimetry (DSC); hot melt extrusion (HME)