Eihei Fukuoka

Analysis of Mean Disintegration Time and Mean Dissolution Time by Moment Analysis Using Microcalorimetric Curves

The mean disintegration time (MDGT; mean time required for disintegration of tablets) and mean dissolution time (MDST; mean time required for drug dissolution) of water-soluble drugsfrom solid dosage forms were determined by moment analysis using microcalorimetric curves. Microcalorimetric curves for heat of dilution and for heat of dissolution of the drug were prepared, and the zeroth and first moments of the calorimetric curves were then calculated. The difference between the first moments of the curves for powder dissolution and tablet dissolution was taken to be the MDGT. The difference between the first moment of the curve for heat of dilutionand that of the curve for heat of dissolution was taken to be the MDST. Nicotinic acid and D-mannitol were used as model drugs. The dissolution rate was determined by the conventional beaker method and also by the deconvolution method. The dissolution process could betraced well by moment analysis, as well as by the other methods employed. Moment analysis has some advantages: (a) both the MDGT and the MDST can be determined simultaneously; (b) it is applicable to many drugs that are soluble with heat evolution without the need for quantitative analysis of the drug.

Evaluation of paracrystalline lattice distortion by profile analysis using a single X-ray diffraction peak

Abstract A method of analyzing the paracrystalline lattice distortion and the size of crystallites was investigated by X-ray powder diffraction. This method was based on Fourier analysis of X-ray diffraction peaks and only a single peak was required for the analysis. The observed peak profiles were well described in split pseudo-Voigt function. After correction for the instrumental broadening, the Fourier coefficients for pure diffraction peak profiles were calculated. The size of the crystallites were calculated from the initial slope of the Fourier cosine coefficients at a harmonic number of 0; then the paracrystalline lattice distortion was evaluated from the extinction curve of the Fourier cosine coefficients. Crystalline powders of griseofulvin, tolbutamide and acetazolamide were used for the model drugs. In the griseofulvin powder, the paracrystalline lattice distortion increased and the size of the crystallites decreased with the grinding time. By the single-peak method, the paracrystalline lattice distortion was underestimated while the size of crystallites was overestimated, compared with those obtained by the multiple-peak method reported previously.