Cyclodextrin-drospirenone inclusion complexes
AssigneeSchering Corporation
InventorsThomas Backensfeld, Wolfgang Heil, Ralph Lipp
Life of this patent
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Abstract
Pharmaceutical compositions comprising low doses of sensitive complexes between an estrogen and a cyclodextrin are provided with improved stability. In specific embodiments the composition comprises a complex between ethinyl estradiol and β-cyclodextrin in a granulate preparation and in yet another embodiment the composition comprises a limited amount of polyvinylpyrrolidone since this excipient was found to degrade ethinyl estradiol. Furthermore, a method for improving the stability of an estrogen in a composition and for manufacturing such a stable composition is provided. Essentially, the granulate preparation are manufactured under careful control of the relative humidity.
Claims32
A composition comprising:
- i) a granulated preparation comprising a complex between an estrogen and a cyclodextrin;
- and
- ii) optionally, one or more excipients,
- the composition having a stability such that said estrogen is in an amount of at least 90% w/w in relation to the initial content of said estrogen after storage for 12 months at 40° C. and 75% relative humidity (RH);
- and
- the composition being essentially free of polyvinylpyrrolidone.
A method for improving the stability of an estrogen in a pharmaceutical composition that comprises an estrogen and one or more excipients in a granulate preparation, which method comprises:
- i) forming a complex between said estrogen and a cyclodextrin;
- and
- ii) granulating the complex to provide the granulate preparation;
- provided that, the composition is prepared so that it is essentially free of polyvinylpyrrolidone.
A process for manufacturing a granulate preparation comprising a complex between an estrogen and a cyclodextrin, which comprises:
- i) loading the complex, optionally one or more other therapeutically active agent(s), and one or more excipients into a granulator;
- ii) applying a liquid onto the loaded complex and the one or more excipients, and
- granulating and drying, so as to obtain granules having a relative humidity not exceeding 60%, as determined at a temperature between 20° C. and 40° C.
Dependencies are inferred from the claim text.