Comparative Evaluation of Mean Particle Size of Bulk Drug Powder in Pharmaceutical Preparations by Fourier-Transformed Powder Diffuse Reflectance Infrared Spectroscopy and Dissolution Kinetics

Abstract

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 (Sw) obtained by the BET N2 gas absorption method or the reciprocal of mean particle size (D50) obtained by particle counting of SEM photomicrographs of ground samples showed straight lines, indicating that the absorbance followed the equation log (l0ll) = K1/D50 = K2SW, where /0 and / are intensities of the incident and transmitted light, respectively, and K1 and K2 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 Sw or the reciprocal of D50 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 °C. The data from initial rates of dissolution of the binary mixture was utilized to calculate the particle size (Dg) using the Hixon-Crowell equation, and these particle size values were consistent with those obtained from Sw data as well as the absorbance data by the IR spectral method.