The Role of Excipients in the Control of Dehydroepiandrosterone Inclusion Complex Delivery

Twenty-five formulations were prepared containing dehydroepiandrosterone (prasterone, DHEA) in the chemical form of inclusion complex with α-cyclodextrin (c-DHEA, 57.30% w/w). The drug was mixed with three different excipient systems: the first “fast” one was a mixture of two disintegrants (Avicel PH 101 and Explotab, at prefixed 4.15 weight ratio); the second “gelling” excipient contained two gel-forming agents (Kollidon PK30 and Methocel K4M) at three weight ratios: 0.31 (A) - 1.00 (B) - 2.45 (C). The third type of “binary” mixture was prepared by combining “fast” and “gelling” systems at three weight ratios: 1:2 – 1:1 – 2:1. Tablets were prepared by direct compression or after wet granulation of these formulations and identified by the same symbols. “Fast” tablets induced a rapid release of the drug while “gelling” tablets were found to modify the release, according to composition. A release profile, characterized by an initial phase of rapid drug release, followed by a period of slower release is achieved with “binary” 1:1 tablets. Series 1:2 tablets provide linear release of the drug; while an undifferentiated release profile was found for series 2:1 tablets. Different release mechanisms and control of drug release are thus obtained by using DHEA as inclusion complex and varying the weight ratios between the different compounds forming the excipients.