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10 protocols using kollidon k30

1

Cinnarizine Solubility Enhancement Using Polymer Blends

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Kolliphor EL (K-EL), Soluplus, and polyvinylpyrrolidone (PVP: Kollidon K30 and K90) were obtained from BASF (Ludwigshafen, Germany). Imwitor 308 (I308) was generously donated by Sasol Germany GmbH (Werk, Witten, Germany). Avochem (Cheshire, UK) supplied the oleic acid (OL). FDC Limited (Maharashtra, India) provided cinnarizine (CN, purity > 99.5%). Capsugel (Morristown, NJ, USA) generously provided fish gelatin size 0 capsules. Grace (Worms, Germany) provided Syloid® SP 53D-11786 (SYL, amorphous magnesium alumino-metasilicate). JRS Pharma (Rosenberg, Germany) supplied the Vivapharm® Hydroxy-propyl methyl cellulose (HPMC) E3. Neusilin® grades US2 and UFL2 were donated by Fuji Chemical Industries (Osaka, Japan).
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2

Ivacaftor Formulation Development and Characterization

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Ivacaftor was acquired from Nexconn Pharmatechs Ltd. (Shenzhen, China). Shin-Etsu Aqoat® (Hypromellose Acetate Succinate) LMP were donated by Shin-Etsu, while Kollidon K30 (PVPK30) was donated by BASF Pharma. Biorelevant dissolution powder (FaSSIF/FeSSIF/FaSSGF) was obtained from Biorelevant Ltd. (London, UK). Sodium lauryl sulfate (SLS), NaCl, Na2SO4, microcrystalline cellulose, and croscarmellose were purchased from Fischer Scientific. Otherwise, ACS or equivalent grade chemicals were used. All compositions are weight by weight (w/w), unless otherwise specified.
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3

Excipient Evaluation for Tablet Formulations

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Microcrystalline cellulose (Avicel PH101, Avicel PH105, Avicel PH301, FMC Biopolymer, Philadelphia, USA), αlactose monohydrate (Pharmatose 200M, Pharmatose 350M, DFE Pharma, Goch, Germany; GranuLac 200, Meggle Group, Wasserburg, Germany), mannitol (Parteck M200, Parteck Delta M, Merck, Darmstadt, Germany) and dicalcium phosphate anhydrous (FCC grade, Innophos, New Jersey, USA) were chosen as fillers. The investigated binders were hydroxypropyl methylcellulose (Pharmacoat 603, Pharmacoat 606, Pharmacoat 615, Shin Etsu, Tokyo, Japan), polyvinylpyrrolidone (Kollidon K30, Kollidon K90F, BASF, Ludwigshafen, Germany), hydroxypropyl cellulose (Klucel LF, Ashland, Kentucky, USA), vinylpyrrolidone-vinyl acetate copolymer (Kollidon VA64, BASF, Ludwigshafen, Germany), fully pregelatinized potato starch (Prejel PA5 PH, DFE Pharma, Goch, Germany) and maltodextrin (Maltrin 150M, Grain Processing Corporation, Iowa, USA).
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4

Formulation Development of RVP Tablets

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RVP powder (purity >99%) and Revanex® tablets containing 200 mg RVP were supplied by Yuhan (Seoul, Korea). Aerosil® 200 was supplied by Evonik Degussa GmbH (Frankfurt am Main, Germany). Avicel PH 101, Brij L4 (BL4), Tween® 20, and Tween® 80 were purchased from Sigma-Aldrich (St. Louis, MO, USA). Florite PS-10 (FLO; calcium silicate) was purchased from Tomita Pharmaceutical Co., Ltd. (Tokushima, Japan). Gelucire 44/14 (G44), Labrafil® M 1944 CS, Labrasol®, and Lauroglycol® 90 were gifted by Gattefossé (Saint Priest, France). Kolliphor® EL, Kolliphor® RH40, Kolliphor® RH60, Kollidon K30, Kollidon K90, Poloxamer (P)188, and P407 were obtained from BASF (Ludwigshafen, Germany). Low-substituted hydroxypropyl cellulose B1 (L-HPC) was supplied by Shin-Etsu Chemical Co., Ltd. (Tokyo, Japan). Neusilin® US2 (magnesium aluminometasilicate) was supplied by Fuji Chemical Industry Company (Toyama, Japan). Sylysia® 350 (porous silica) was supplied by Fuji Silysia Chemical Co., Ltd. (Aichi, Japan). Vivapur (VP)12 and VP105 were supplied by JRS Pharma (Rosenberg, Germany). High-performance liquid chromatography (HPLC)-grade methanol was purchased from JT Baker (Phillipsburg, NJ, USA). All other chemicals used were of analytical grade.
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5

Gefitinib Permeability in Caco-2 Cells

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Gefitinib (ZD) (ZD1839) was purchased from Med Chem Express Co., Ltd. (Shanghai, China). The Caco-2 cell line, trifluoroacetic acid (TFA), foetal bovine serum (FBS), thiazolyl blue tetrazolium bromide, l-glutamine-penicillin-streptomycin solution, dimethyl sulfoxide (DMSO), Eagle’s minimum essential medium (EMEM), trypsin-EDTA solution, trypan blue solution (0.4%), neutral red and actinomycin D were all purchased from Sigma-Aldrich (Dorset, UK). Acetone, sodium hydroxide and absolute ethanol were obtained from VWR International (Leicestershire, UK). Hydrochloric acid, Dulbecco’s phosphate-buffered saline (PBS), sodium chloride, Dulbecco’s modified Eagle’s medium (DMEM), potassium dihydrogen orthophosphate, acetic acid glacial and Nunclon 96-well microplates were purchased from Fisher Scientific UK Ltd. (Loughborough, UK). Eudragit S 100 was provided by Evonik Röhm Gmbh (Essen, Germany). Kollidon K 30 (PVP) was kindly donated by BASF SE (Ludwigshafen, Germany). HPMC 603 (HPMC) was kindly given by Shin-Etsu Chemical Co., Ltd. (Tokyo, Japan).
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6

Optimization of Cinnarizine Solid Dispersions

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Imwitor 308 (I308, Glyceryl Caprylate, monoglycerides ≥ 80%) was kindly supplied by Sasol Germany GmbH (Werk Witten, Germany). Oleic acid (OL, long chain fatty acid C18:1) was obtained from Avonchem (Cheshire, UK). Cremophor EL (Cr-El, polyoxyl 35 castor oil) was supplied by BASF (Ludwigshafen, Germany). Cinnarizine (CN, purity > 99.5) was supplied by FDC Limited (Maharashtra, India). Fish gelatin capsules (size 0) were donated by Capsugel (Morristown, NJ, USA). Vivapharm® Hydroxy-propyl methyl cellulose (HPMC) E3, was purchased from JRS Pharma (Rosenberg, Germany). Kollidon K30® (Polyvinylpyrrolidone, PVP) was donated by BASF (Ludwigshafen, Germany). Pluronic F127 (PL-127, polyoxyethylene-polyoxypropylene block co-polymer) was purchased from Sigma Aldrich, St. Louis, MO, USA. Neusilin® US2 (amorphous magnesium aluminometasilicate) was obtained from Grace (Worms, Germany).
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7

Posaconazole Amorphous Solid Dispersions

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Posaconazole (POS, > 99.5% purity, 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)tetrahydro- 5-(1H-1,2,4-triazol-1-ylmethyl)-3-furanyl]methoxy]phenyl]-1-piperazinyl]phenyl]-2-[(1S,2S)-1-ethyl- 2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one, Wuhan ChemNorm Biotech Co., Ltd., Wuhan, China) was used as a model drug. Two amorphous polymers, i.e., Kollidon K30 (K30, poly(vinylpyrrolidone), and Kollidon VA64 (KVA, poly(vinylpyrrolidone-vinyl acetate)), both from BASF, Ludwigshafen am Rhein, Germany, and two semi-crystalline polymers, Kollicoat IR (KIR, Macrogol poly(vinyl alcohol)Grafted Copolymer, BASF, Ludwigshafen am Rhein, Germany), and Parteck MXP (PXP, poly(vinyl alcohol), Merck KGaA, Darmstadt, Germany) were used as polymeric matrices for ASD. The physical mixtures, containing crystalline POS and one of the listed polymers in concentrations from 10 to 70 wt.% of the polymer, were prepared by co-mixing the appropriate amount of the materials inside an agate mortar. The binary systems, containing an amorphous form of POS, were obtained after the physical mixture’s melt quench. The water used in all tests was produced by an Elix 15UV Essential reversed osmosis system (Merck KGaA, Darmstadt, Germany). All other reagents were of the analytical grade.
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8

Felodipine Sustained-Release Formulation

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Felodipine (Nivedita Chemicals PVT Ltd, India); lactose monohydrate (LM) (Pharmatose 80M and Pharmatose 200M, DMV International, Holland) and microcrystalline cellulose (MC) (Vivapur 101 and Vivapur 102, JRS Pharma, Germany) were used as diluents; polyvinylpirrolidone – PVP (Kollidon K30, BASF, Germany) was used as binder; aqueous dispersion of ethyl acrylate and methyl methacrylate (Eudragit NE 40D, Evonix, Germany), acrylate, methyl methacrylate and a low content of methacrylic acid ester with quaternary ammonium groups (Eudragit RS 30D, Evonix, Germany), aqueous ethyl-cellulose dispersion (Surelease E719040, Colorcon, UK) were used as film forming polymers and low viscosity hydroxipropylmethylcellulose; HPMC (Methocel E5LV, Colorcon, U.S.A.) was used as a pore forming agent in the polymeric coating; triethyl citrate; TEC (Merck, Germany) was used as plasticizer in the polymeric coating. All the other substances used in this research were analytic grade from Merck, Germany.
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9

Formulation and Characterization of Tablet Excipients

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Microcrystalline cellulose (Avicel PH101, Avicel PH105, Avicel PH301, FMC Biopolymer, Philadelphia, USA), α-lactose monohydrate (Pharmatose 200M, Pharmatose 350M, DFE Pharma, Goch, Germany and GranuLac 200, Meggle Group, Wasserburg, Germany) and mannitol (Parteck M200, Parteck Delta M, Merck, Darmstadt, Germany) were used as fillers. Hydroxypropyl methylcellulose (Pharmacoat 603, Shin Etsu, Tokyo, Japan) and polyvinylpyrrolidone (Kollidon K30, BASF, Ludwigshafen, Germany) were used as binders in this study. Croscarmellose sodium (Disolcel GF, Mingtai Chemical Co, Taoyuan Hsien, Taiwan), magnesium stearate (Mallinckrodt, St. Louis, USA) and colloidal silicon dioxide (Aerosil 200, Evonik, Rheinfelden, Germany) were used to prepare the final blend for tablet compression.
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10

Optimizing Grape Seed Extract Formulation

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RSV from grape seed (98%) was purchased from Thanen Chem (Changzhou, China). Kolliphor EL, Kolliphor P188, Kolliphor P407, Kolliphor RH40, and Kollidon K30 were obtained from BASF (Ludwigshafen, Germany). Propylene glycol, polyethylene glycol (PEG) 400, acetone, methanol, dichloromethane, ethanol, and ammonium carbonate were obtained from Merck (Darmstadt, Germany). Tween 80 and HPMC K100LV were obtained from Sigma Aldrich (St. Louis, MO, USA) and Colorcon (West Point, PA, USA), respectively. Mannitol was obtained from Roquette (Lestrem, France)
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