Comparative evaluation of mean particle size of bulk drug powder in pharmaceutical preparations by Fourier-transformed powder diffuse reflectance infrared spectroscopy and dissolution kinetics

This paper reports a quantitative correlation between specific FT-IR absorption peak intensity of phenytoin (PTH) to its particle size in the bulk as well as in powder blends. Absorption peak intensity in FT-IR spectra of phenytoin (PHT) increased with decrease of mean particle size of the powders. The relationships between the FT-IR absorbance at 1724 cm(-1) of PHT and the specific surface area (S-w) obtained by the BET N-2 gas absorption method or the reciprocal of mean particle size (D-50) obtained by particle counting of SEM photomicrographs of ground samples showed straight lines, indicating that the absorbance followed the equation log (l(o)/I) = K-1/D-50 = K2Sw, where I-o and I are intensities of the incident and transmitted light, respectively, and K-1 and K-2 are constants. In binary mixture of powders containing 50% PHT and 50% lactose, the relationship between the absorbance at 1724 cm(-1) of PHT powder and S-w or the reciprocal of D-50 also gave a linear plot. The dissolution behaviors of the binary mixture samples were measured in pH 1.2 buffer containing 0.1% sodium lauryl sulfate at 37 degrees C. The data from initial rates of dissolution of the binary mixture was utilized to calculate the particle size (D-g) using the Hixon-Crowell equation, and these particle size values were consistent with those obtained from S-w data as well as the absorbance data by the IR spectral method.