A Dissolution Method for Hard and Soft Gelatin Capsules Containing Testosterone Undecanoate in Oleic Acid

Abstract

A convenient and reproducible dissolution method for soft and hard gelatin capsules containing testosterone undecanoate in oleic acid is described. The method uses a flowthrough dissolution cell and a dissolution medium the composition of which was optimized for both its capacity to dissolve the gelatin capsule wall completely and to give homogeneous filtrates of drug and oily excipient for convenient analysis of the collected fractions.

The discriminating power of the dissolution method for oily formulations of testosterone undecanoate was tested with three batches of the commercial formulation Andriol^R, and with two experimental formulations. The three batches of AndriolR, soft gelatin capsules containing testosterone undecanoate in pure oleic acid, displayed biphasic dissolution patterns while dissolutions were always complete within 45 minutes. Dissolution of testosterone undecanoate from the experimental capsule formulation containing oleic acid and beeswax took about 3 hours to complete, whereas only 20% of testosterone undecanoate dissolved in the same time from the experimental capsule formulation containing a thixotropic mixture of oleic acid, beeswax and silicon dioxide.

In a study in healthy male volunteers it was found that the fast dissolving Andriol^R capsules gave peak plasma levels above the normal upper limit of testosterone plasma concentrations, whereas the slowly dissolving pasty hard gelatin capsules gave values within the normal range of testosterone plasma concentrations. The described dissolution method could therefore provide a promising approach to the development of new oily formulations of testosterone undecanoate with other invivo characteristics than those of Andriol^R.