Development of a sustained-release matrix tablet formulation of DHEA as ternary complex with alpha-cyclodextrin and glycine

Sustained-release matrix-tablets of dehydroepiandrosterone (DHEA) as ternary complex with a-cyclodextrin and glycine (c-DHEA) were prepared by direct compression with suitable excipients. The influence of the swelling properties of hydroxypropylmethylcellulose (HPMC) and the disintegrating power of Explotab used in combination, as well as the effect of the presence, type and amount of suitable channelling agents (Emcocel and spray-dried lactose, alone or in combination) on drug release behaviour from matrix-tablets has been evaluated.The best performances in terms of drug release was obtained from formulations containing a 75:25 w/w spray-dried lactose: Emcocel combination in the presence of HPMC as matrix-forming polymer, leading to a more than 65% DHEA released at the end of the test, a value which was, respectively, 1.9 and 2.7 times higher than those achieved with the corresponding formulations containing spray-dried lactose or Emcocel alone. The drug release profile from the most effective matrix tablet formulation of c-DHEA allowed achievement of a more than 6-fold increase in the drug amount released within 24 h in comparison with the same formulation containing the simple physical mixtures of DHEA, a-cyclodextrin and glycine. Therefore the advantage of using DHEA as ternary complex, prepared by mechano-chemical treatment, was clearly demonstrated, thus allowing the development of an effective sustained-release formulation of the drug.