Liquid nitrogen

OLZ was a gift from Rampex Labs Pvt. Ltd. (Telangana, India). SAC (Sigma-Aldrich, Steinheim, Germany) was used as the co-former and dichloromethane (Biochem Chemopharma, Cosne sur Loire, France) as the solvent for the preparation of OLZ-CAM. Liquid nitrogen (Air Liquide, Lisbon, Portugal) was used to prepare amorphous OLZ. Tablets were manufactured from blends of OLZ and SAC, dibasic calcium phosphate anhydrous (DI-CAFOS^® A60, a gift from Budenheim, Budenheim, Germany), microcrystalline cellulose (Avicel PH-101, FMC Corp., Cork, Ireland), polyvinylpyrrolidone (K25, BASF, Ludwigshafen, Germany) and croscarmellose sodium (JRS Pharma, Rosenberg, Germany). Demineralized water (Destillo 2, Herco, Freiberg am Neckar, Germany), sodium hydroxide (Eka, Marietta, GA, USA), and potassium phosphate monobasic (Carlo Erba Reagents, Val de Reuil, France) were used to prepare the phosphate buffer (pH 8.0) for the dissolution studies. Marketed tablets of OLZ (15 mg, Generis Farmacêutica, S.A., Amadora, Portugal) were used as controls in the dissolution studies. A desiccator containing magnesium nitrate (53% RH, ThermoFisher GmbH, Kandel, Germany) was used to store amorphous OLZ and OLZ-CAM.

All-trans-β-carotene (Type II synthetic, purity >95%), lutein from marigold, β-cryptoxanthin (purity >97%), zeaxanthin (purity >95%), lycopene from tomato (purity >90%), butylhydroxytoluene (BHT, purity ≥99%) and triethylamine (TEA, purity ≥99%) were obtained from Sigma-Aldrich (Shnelldorf, Germany). High-performance liquid chromatography (HPLC) organic solvents were of analytical grade: methanol (MeOH), absolute ethanol (EtOH), chloroform and hexane were from Carlo Erba (Val-de-Reuil, France), methyl-tert-butyl-ether (MTBE) was from Fisher Scientific (Loughborough, UK), petroleum ether (PE) was from VWR Prolabo (Fontenay-sous-Bois, France). Ultrapure water was obtained from a purified water system Arium^® 611UV from Sartorius (Göttingen, Germany) with a resistivity of 18.2 MΩ*cm. Sodium chloride (NaCl, purity >99%) and potassium hydroxide (KOH, purity >99%) were obtained from VWR Prolabo (Fontenay-sous-Bois, France), and activated magnesium silicate Florisil^® at 100–200 mesh (Sigma-Aldrich, Shnelldorf, Germany). Liquid Nitrogen was from Air Liquide (Nancy, France). The synthesis of 5-(4-carboxyphenyl)-10,15,20-triphenyl porphyrin (P1COOH) has been described elsewhere [25 (link)].

OLZ (polymorphic form I, melting point 192.4 °C [35 (link)]) was used as a model drug (Rampex Labs Pvt. Ltd., Telangana, India). For the preparation of amorphous OLZ, liquid nitrogen (purity ≥ 99.8%, Air Liquide, Lisbon, Portugal) was used to rapidly quench the molten drug. For the preparation of OLZ-CAM, SAC was used as co-former (Sigma-Aldrich, Steinheim, Germany) and dichloromethane was used as solvent (Biochem Chemopharma, Cosne sur Loire, France). To produce granules and pellets, OLZ was incorporated in a formulation made of dibasic calcium phosphate anhydrous (DI-CAFOS^® A60, Budenheim, Budenheim, Germany), microcrystalline cellulose (Avicel PH-101, FMC Corp., Cork, Ireland) and polyvinylpyrrolidone (K25, BASF, Ludwigshafen, Germany). Demineralized water, used as granulation liquid, was obtained using a Destillo 2 apparatus (Herco, Freiberg am Neckar, Germany). Hard gelatin capsules (size 0) were acquired from Lonza (Basel, Switzerland). To prepare the pH 8.0 phosphate buffer for the dissolution studies, demineralized water (Destillo 2 apparatus, Herco, Freiberg am Neckar, Germany), sodium hydroxide (Eka Chemicals Inc., Marietta, GA, USA) and potassium phosphate monobasic (Carlo Erba Reagents, Val de Reuil, France) were used.