Steroid monohydrates, formulations containing same and method
AssigneeE. R. Squibb & Sons, Inc.
InventorsYu-Chang J. Wang, Dursch Friedrich, Richard L. O'Laughlin, Thaddeus Prusik
Life of this patent
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Abstract
A monohydrate of a steroid having the structure ##STR1## and the 1,2-dehydro derivatives thereof, is provided which monohydrate is in the form of a particulate material having a stable average particle size of less than about 20 microns. Cream and lotion formulations containing the steroid monohydrate and a method for forming the monohydrate are also provided.
Claims14
A method for forming the monohydrate of a steroid, said monohydrate having an average particle size of less than about 20 microns, said steroid having the structure ##STR8## wherein R.sub.1 is chlorine, fluorine or hydroxy and R'.sub.1 is hydrogen or R.sub.1 and R'.sub.1 together are .dbd.O;
- R.sub.2 is hydrogen or halogen;
- R.sub.3 is hydrogen, methyl or fluorine;
- R.sub.4 is hydrogen, hydroxy, ##STR9## or halogen;
- and R.sub.5 and R.sub.6 are the same or different and are hydrogen, alkyl, alkylthio, alkoxy, carboalkoxy, formyl, ##STR10## hydroxy, halogen, phenyl or cyano, with the proviso that when R.sub.5 and R.sub.6 are different, one of R.sub.5 and R.sub.6 is hydrogen, which method includes the steps of micronizing the steroid in anhydrous form, introducing the micronized anhydrous steroid into water to hydrate the steroid to form the corresponding monohydrate and cause crystal growth, reducing the average particle size of the crystals of hydrated steroid suspended in water to below about 25 microns to form particles of steroid monohydrate having a relatively stable crystal size.
A method for forming the monohydrate of a steroid, said monohydrate having an average particle size of less than 20 microns, said steroid having the structure ##STR11## wherein R.sub.1 is chlorine, fluorine or hydroxy and R'.sub.1 is hydrogen or R.sub.1 and R'.sub.1 together are .dbd.O, R.sub.2 is hydrogen or halogen;
- R.sub.3 is hydrogen, methyl or fluorine;
- R.sub.4 is hydrogen, hydroxy, ##STR12## or halogen;
- and R.sub.5 and R.sub.6 are the same or different and are hydrogen, alkyl, alkylthio, alkoxy, carboalkoxy, formyl, ##STR13## hydroxy, halogen, phenyl or cyano, with the proviso that when R.sub.5 and R.sub.6 are different, one of R.sub.5 and R.sub.6 is hydrogen, which method includes the steps of micronizing the steroid in anhydrous form and subjecting the micronized anhydrous steroid to a relative humidity of higher than 40% for a period of at least about 4 hours to form a monohydrate of the steroid while controlling and limiting crystal size of the steroid monohydrate.
Dependencies are inferred from the claim text.