Naokazu Murahashi

Evaluation of the crystalline and amorphous states of drug products by nanothermal analysis and Raman imaging.

In recent years, amorphous formulations and other special dosage forms of drug products have been investigated to achieve adequate solubility and disintegration. We have evaluated the distribution of crystalline and amorphous states of a drug product using Nanothermal analysis (Nano-TA) and Raman imaging methods. Compared to conventional differential scanning calorimetry, Nano-TA can be used to more rapidly characterize the crystalline and amorphous states of model formulations, including their ingredient distributions, without any sample preparation. In the current study, imaging maps obtained for specific model formulations were evaluated on the basis of their visual appearance and the physicochemical properties of the active pharmaceutical ingredient (API). In addition, the crystalline and amorphous states of the model formulations were distinguished by Raman mapping. Nano-TA was found to be useful for the characterization of crystalline and amorphous states of APIs and the distribution of other ingredients. This technology could be used to monitor the changes in crystalline forms of drug substances and dosage forms during processing. In addition, Nano-TA can be used to characterize amorphous states.

Rectal Absorption of E-2078 (Dynorphin Analogue Peptide) in Rats

Abstract— The plasma levels in rats of a dynorphin analogue peptide (E‐2078) after rectal administration have been studied. The bioavailabilities of E‐2078 after rectal administration, subcutaneous injection, intramuscular injection, and oral administration were 21·6, 67·8, 67·1, 0·7%, respectively. The effect of dose, pH, osmolarity and viscosity on the rectal absorption of E‐2078 were studied. A sigmoid relationship between the dose and the AUC was observed on rectal administration, while there was a linear relationship on intramuscular administration. The AUC was increased in acidic solution and highly viscous solution. The osmolarity did not affect the absorption of E‐2078. In microscopic studies, E‐2078 caused little or no damage to the rectal mucosa in rats.

Characterization of the Physicochemical Properties of the Micelles of Platelet-Activating Factor (C18:0)

The purpose of this study was to clarify the physicochemical properties of the micelles of platelet-activating factor (PAF; C18:0). The critical micelle concentration (CMC) of PAF (C18:0) was determined (0.20 μM) using fluorescence techniques. The fluidity and the micropolarity of the PAF (C18:0) micelle were similar to those of the micelle of stearoyl lysophosphatidylcholine.

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.

A temperature study on critical micellization concentration of the novel platelet-activating factor receptor antagonist E5880 in water by electric conductivity measurements.

To clarify the behavior of the novel platelet-activating factor (PAF) receptor antagonist E5880 in aqueous solution, electric conductivity was measured at different temperatures (every 5°C), ranging from 15°C to 50°C. Critical micellization concentration (CMC) of E5880 was dependent on the temperature; at 30°C, the CMC value was smallest (0.143 mM). Below that temperature, the enthalpy for formation of the micelle (Δ H0m) was positive, and the formation of micelles was endothermic; above that temperature, Δ H0m was negative, and the formation of micelles was exothermic.