ABSTRACT
The novel anticancer agent BIBX1382BS is a representative of the human epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. BIBX1382BS, for parenteral use, is formulated pharmaceutically as a lyophilized product containing 100 mg BIBX1382BS per dosage unit. This in vitro study was performed to establish the optimal intravenous administration conditions (infusion concentration and infusion rate) for the forthcoming clinical absolute oral bioavailability study of BIBX1382BS. BIBX1382BS infusion solutions have a low pH in order to keep the substance in solution. We therefore decided to investigate the hemolytic and precipitation potential of the drug in vitro. Also, the ratio of formulation (F) solution volume and a blood simulans (B) volume necessary to reach the physiological pH, expressed as the FB-ratio, was determined in vitro. On the basis of the results obtained, it is advised to administer BIBX1382BS infusion at a concentration of 1 mg/ml and a maximum infusion rate of 10 ml/min. This article describes the in vitro biocompatibility screening program.
Subject(s)
Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , ErbB Receptors/antagonists & inhibitors , Organic Chemicals , Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/pharmacology , Chemical Precipitation , Hemolysis/drug effects , HumansABSTRACT
The average degree of substitution of mixtures of hydroxypropyl-beta-cyclodextrin derivatives has a large influence on the complexing abilities and physiochemical properties of the derivatives. A low degree of substitution is preferable, since these derivatives show the best complexing properties and, at the same time, low surface activities.
Subject(s)
Cyclodextrins/analysis , Dextrins/analysis , Starch/analysis , Chemistry, Pharmaceutical , Chromatography, High Pressure Liquid , Surface PropertiesABSTRACT
The effect of γ-cyclodextrin and its four derivatives on the solubility of progesterone in phosphate buffer pH 7.4 was investigated. γ-Cyclodextrin forms a complex precipitating from solution at low cyclodextrin concentrations. No precipitation of complexes was observed with the γ-cyclodextrin derivatives. This change in phase-solubility behavior is probably due to low crystallization tendencies of the derivatives.
