Plasdone s 630

Kollidon^® VA-64 (copovidone, VA64), Soluplus^® (Poly(vinyl caprolactam-covinylacetate-ethylene glycol) graft polymer, SOL), and Kolliphor^® RH40 (PEG-40 Hydrogenated Castor Oil) were received from BASF SE (Ludwigshafen am Rhein, Germany). Plasdone^® S-630 (PVPVA64, PL_630) and Plasdone^® S-630 Ultra (PVPVA64, PL_630U) were delivered from Ashland Inc. (Düsseldorf, Germany). Capmul^® MCM EP (Glycerol Monocaprylocaprate Type I EP) was provided by Abitec Corp (Janesville, WI, USA). Transcutol^® (diethylene glycol monoethyl ether) and Labrafac^® lipophile WL 1349 (medium chain triglycerides) were received from Gattefossé (Saint-Priest, France).

CHR (purity > 99%) was purchased from DASF Biotechnology (Nanjing, China). Plasdone^® S630 (PL-S630) was obtained from Ashland (Wilmington, NC, USA). Tween 80 was purchased from Xilong Chemicals (Shantou, China). HPLC-grade methanol and acetonitrile were supplied by Merck KGaA (Darmstadt, Germany). All aqueous solutions were prepared using Milli-Q^® water (resistivity > 18 MΩ·cm). All other chemicals used were at least of analytical grade.

Powdered CE containing 20% of TB (lot CAC01) was obtained from Badmonkeys Botanicals (Tacoma, WA, USA). TB (lot BCBM9560V, >98.5%) was purchased from Sigma-Aldrich (Steinheim, Germany). The polymer Plasdone^® S-630 (lot 0001810863, poly(vinylpyrrolidone-co-vinylacetate); PVP) was kindly provided by Ashland Specialty Ingredients (Covington, LA, USA); Soluplus^® (lot 844143368EO, polyvinylcaprolactam-polyvinylacetate-polyethyleneglycol, Sol) was donated by BASF (Ludwigshafen, Germany); and Eudragit^® E PO (lot G130531504, butyl methacrylate: dimethylamino ethyl methacrylate: methyl methacrylate 1:2:1, EuE) was donated by the Evonik Corporation (Essen, Germany). All other chemicals and solvents were of analytical grade.

Three pharmaceutical polymers commonly used in hot melt extrusion were utilized in this study [9 (link),17 (link),18 (link)]. These were chosen based on the different rheological behavior of their melts [19 ,20 (link)]: Polyvinylpyrrolidone vinyl acetate (PVPVA) (Plasdone S-630, Ashland Inc., Columbus, OH, USA); the commonly utilized graft copolymer, Soluplus (SOL) (BASF SE, Ludwigshafen, Germany); and the basic butylated methacrylate copolymer (bBMA) (Eudragit EPO, Evonik Industries AG, Darmstadt, Germany). The material densities were determined with a helium pycnometer (Micro UltraPyc 1200E, Quantachrome, Baynton Beach, FL, USA) and bulk densities (untapped densities) were determined using a tapped density tester (Sotax TD1, Sotax, Aesch, Switzerland) in accordance with the European Pharmacopoeia [21 ].

The graphene oxide (GO) powder was purchased from SIGMA ALDRICH (796,034) and employed without any further purification. 1 g of GO powder (12 mg mL⁻¹ dispersion) was mixed with 120 mL of isopropanol (MERCK) and 3 g of a 3:2 copolymer of N -vinyl-2-pyrrolidone (NMP, SIGMA ALDRICH) and vinyl acetate (PLASDONE S-630, ASHLAND INC., USA) to constitute GO: binder weight ratio of 1:3, and obtained a thick black slurry. The thick slurry was further sonicated using a stainless steel-based probe sonicator for 1 h. This was carried out under constant cooling with iced water, within a few minutes of mixing at 2000 rpm the slurry converts into a homogeneous dispersion, which is then subjected to treatment at 5000 rpm. This dispersion was passed through a 3.1 μm glass fiber filter membrane (ACRODISC)^{60 (link)}. Further, the dispersion was mixed with 1.5 g ethyl cellulose (SIGMA ALDRICH) in 10 ml of ethanol. After adding 1 mL terpinol (SIGMA ALDRICH) to the blend, it was stirred thoroughly and subsequently dried off the ethanol from the solution in a vacuum oven to obtain a viscous GO paste.