Optimization of the formulation and characterization of the physicochemical properties of the novel platelet-activating factor receptor antagonist E5880.
The injectable formulation of E5880, a novel platelet-activating factor (PAF) receptor antagonist, was determined from the study of pH stability, the selection of excipient, and the relationship between moisture and stability. The physicochemical properties of E5880 in the optimized formulation (0.6 mg/ml of E5880, 0.1% [4.8 mM] citric acid, 10% lactose, pH 2.8) were characterized. The critical micelle concentration of E5880 in the buffer was 0.1 mg/ml, and the structure was of spherical micelles. The micellar size was 5.6 nm and did not change before and after lyophilization and storage. The number of the molecules per micelle was 40. The micropolarity around the hydrocarbon region of the micelle was similar to that of butanol.
Asai
Y
Y
Formulation Research Laboratory, Kawashima, Eisai Company, Limited, Gifu, Japan.
Murahashi
N
N
Iwamoto
K
K
D002626:Chemistry, Pharmaceutical; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008823:Micelles; D010880:Piperidines / Q000737:chemistry*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D011726:Pyridinium Compounds / Q000737:chemistry*; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013500:Surface Tension
D005079:Excipients; D008823:Micelles; D010880:Piperidines; D010980:Platelet Membrane Glycoproteins; D011726:Pyridinium Compounds; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; C072429:E 5880