Cyclodextrin-drospirenone inclusion complexes
AssigneeSchering Corporation
InventorsThomas Backenfeld, Wolfgang Heil
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.
Claims46
A formulation comprising a complex between an estrogen and a cyclodextrin, wherein the formulation is a granulate preparation, said granulation preparation having a relative humidity of at most 60%, as determined at a temperature between 20° C. and 40° C.
A composition comprising:
- i) a complex between an estrogen and a cyclodextrin;
- and
- ii) one or more excipients,
- the composition having a stability such that said estrogen is in amount of at least 85% w/w in relation to the initial content of said estrogen after storage for 12 months at 40° C. and 75% relative humidity (RH).
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, the method comprises the steps of:
- i) forming a complex between said estrogen and a cyclodextrin;
- and
- ii) mixing under granulation conditions the said complex with the one or more excipients such that the relative humidity of the final granulate does not exceed 60%, as determined at a temperature between 20° C. and 40° C.
A process for manufacturing a granulate preparation comprising a complex between an estrogen and a cyclodextrin, wherein the processing of the granulate preparation comprises the steps of:
- i) loading the complex, optionally further one or more 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 under granulation conditions 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.