Toyo Capsule Co. Ltd.

Soft capsules may enhance oral absorption and bioavailability of active substances by appropriately combining them with excipients such as lipids and surfactants. However, these excipients affect the determination of active substances and warrant several considerations for establishing optimal analytical methods. The function of mutual information (FUMI) theory is a chemometric tool that estimates the relative standard deviation (RSD) of the peak area by approximating the baseline of a chromatogram with a stochastic process. In this study, we used a dutasteride (DUT) soft capsule as the specimen, and we propose a method to evaluate the RSD of the peak area of active substances in soft capsules based on the FUMI theory. Furthermore, we have established a method to evaluate the RSD of the peak area using a manual method for signal-noise resolution for soft capsules where the excipients interfere with the active substances. RSD (N = 1) obtained using this method was within the 95 % confidence interval of the RSD estimated using repetitive measurements (N = 6). In conclusion, the proposed method enables the efficient evaluation of precision without requiring repetitive measurements.

A dissolution test was performed on a soft-gelatin capsule containing tocopherol nicotinate (TN) diluted with vegetable oil.The test methods were the paddle (PD) method described in the Japanese Pharmacopoeia (JP) and a rotating dialysis cell (RDC) method by which the sample is disintegrated inside a rotating cell covered with a filter and the contents are expelled from the cell into a solution outside.TN is practically insolubleIn the aqueous test solutions (pH 1.2 and 6.8), low dissolution rates were obtained by both the PD and RDC methods.However, the authors obtained a high dissolution rate by adding n-octanol, which has often been used for the measurement of drug partition coefficient, as a modification of the RDC method which has many factors controlling the drug dissolutionBy examining the changes in the blood concentrations of TN after administration of the TN soft-gelatin capsule to humans, the authors established a relationship between the in vivo/in vitro findings.