Bioavailability of Four Oestradiol Suspensions with Different Particle-Sizes - In Vivo/In Vitro Correlation

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Abstract
A comparative bioavailability study was performed, using three specially made particle-size fractions of oestradiol and a sample of oestradiol commercially obtained, all chemically equivalent. Aqueous suspensions of these four fractions were administered orally to five subjects, following a completely randomized cross-over design. The in vitro tests included particle-size analysis, using resistance particle counter and dissolution characterisation, using the Paddle method and also again the resistance particle counter method. The influence of particle size on the initial absorption is clearly significant (p<.01). The influence of particle size on total area (AUC) under the curve, show a weak significance (p<.05). Both in vitro dissolution methods showed clearly different profiles for the four suspensions, which are in agreement with the differences, shown by the size frequency distribution. A good correlation coefficient (0.983) are obtained by comparing particle-size distribution with in vitro release data. In vivo/in vitro correlation was demonstrated by comparing values for AUC and % dissolved from in vitro data. The correlation coefficients was gt; 0.950. The results clearly indicate the great importance of the particle-size distribution for dissolution profiles, and hence for the absorption.