Studies Relating to the Content Uniformity Cif Ethinylo-Estradiol Tablets 10 Ug: Effect of Particle Size of Ethinyloestradiol

Abstract

Ethinyloestradiol is formulated in minute amounts, e. g. 10 μg per tablet of 50 mg weight. Experiments to relate the shape of the distribution curve and the extent of homogeneity to the particle size of ethinyloestradiol were performed.

Results showed that on comparison of values of C_R (the coefficient of variation for a random mix), with C_P and C_t (the coefficients of variation for powder mix and tablets respectively), for the batches containing the large particle size fractions of drug the values are as predicted by random mixing theory. As the particle size of the drug is decreased, the values of C_P and C_t also decrease in accordance with random mixing theory until a critical particle size d_c′ is reached. For batches containing drug particles of size less than d_c′ then both C_P and C_t increase with decreasing particle size. This change is associated with a change to a positively skewed distribution because of the cohesive properties of fine powders and their tendency to form agglomerates which remain undispersed in the excipients. Above d_C′ the rate limiting step in powder mixing is randomisation and below it the rate limiting step in achieving the required homogeneity is the breaking down of the drug agglomerates. In addition to its effects on the magnitude of C_P and C_t, the particle size of ethinyloestradiol has a marked influence on the shape of the distribution curve.