Crystalline form of a vitamin D analogue

Abstract

The present invention relates to calcipotriol hydrate—a new crystalline form of calcipotriol—with superior technical properties and with superior stability.

1. Calcipotriol monohydrate characterized by its storage stability at 40° C. after 12 months, its ready wettability and its suitability for wet ball milling characteristics . 
     
     
       2. Pharmaceutical composition containing the compound  calcipotriol monohydrate of  claim 1 . 
     
     
       3. Pharmaceutical composition according to  claim 2  which is a cream. 
     
     
       4. Pharmaceutical composition according to  claim 2  which is a gel. 
     
     
       5. Pharmaceutical composition comprising calcipotriol monohydrate according to any one of  claim 4   claims  2 - 4  and a pharmaceutically acceptable vehicle, with a content of the active component of  calcipotriol monohydrate being 1-100 μg/g of the composition. 
     
     
       6. The method of preparing calcipotriol monohydrate which comprises dissolving calcipotriol in organic solvent and then adding water to the resulting solution to precipitate the hydrate, said hydrate being characterized by its storage stability at 40° C., its ready wettability and its suitability for wet ball milling characteristics . 
     
     
       7. In the preparation of a gel formulation which involves wet ball milling a calcipotriol component and adding the wet milled calcipotriol component to a gel base, the improvement which comprises wet milling calcipotriol hydrate as said component and using this wet milled hydrate for addition to said gel base, said hydrate being characterized by its storage stability at 40° C. after 12 months, its ready wettability and its suitability for wet ball milling characteristics . 
     
     
       8. Calcipotriol monohydrate according to  claim 1 , wherein said monohydrate exhibits an infrared spectrum which comprises the following characteristic lines based on the potassium bromide technique:
     1455   ( m ) ,  1442   ( m ) ,  1330   ( w ) ,  1290   ( m ) ,  1210   ( m ) ,  1085   ( m ) ,  907   ( m ) ,  895   ( m )  and  573   ( w )  cm   −1   , respectively.     
     
     
       9. Calcipotriol monohydrate according to  claim 1  or  8 , wherein said monohydrate exhibits a solid state CPMAS  13   C NMR spectrum which comprises the following resonances:        147 . 9 ,  146 . 5 ,  134 . 8 ,  130 . 3 ,  129 . 0 ,  126 . 5 ,  116 . 0 ,  109 . 4 ,  75 . 5 ,  68 . 2 ,  67 . 2 ,  56 . 9 ,  55 . 2 ,  47 . 8 ,  47 . 5 ,  42 . 9 ,  42 . 0 ,  41 . 3 ,  30 . 7 ,  28 . 9 ,  25 . 6 ,  23 . 1 ,  22 . 6 ,  19 . 5 ,  14 . 6 ,  6 . 2  and  1 . 9  ppm, respectively.     
     
     
       10. A pharmaceutical composition according to  claim 2 , wherein said monohydrate exhibits an infrared spectrum which comprises the following characteristic lines based on the potassium bromide technique:
     1455   ( m ) ,  1442   ( m ) ,  1330   ( w ) ,  1290   ( m ) ,  1210   ( m ) ,  1085   ( m ) ,  907   ( m ) ,  895   ( m )  and  573   ( w )  cm   −1   , respectively.     
     
     
       11. A pharmaceutical composition according to  claim 2  or  10 , wherein said monohydrate exhibits a solid state CPMAS  13   C NMR spectrum which comprises the following resonances:        147 . 9 ,  146 . 5 ,  134 . 8 ,  130 . 3 ,  129 . 0 ,  126 . 5 ,  116 . 0 ,  109 . 4 ,  75 . 5 ,  68 . 2 ,  67 . 2 ,  56 . 9 ,  55 . 2 ,  47 . 8 ,  47 . 5 ,  42 . 9 ,  42 . 0 ,  41 . 3 ,  30 . 7 ,  28 . 9 ,  25 . 6 ,  23 . 1 ,  22 . 6 ,  19 . 5 ,  14 . 6 ,  6 . 2  and  1 . 9  ppm, respectively.     
     
     
       12. Pharmaceutical composition according to  claim 2  which is an ointment. 
     
     
       13. Pharmaceutical composition according to  claim 2  which is a lotion. 
     
     
       14. Pharmaceutical composition according to  claim 2  which is a solution. 
     
     
       15. Pharmaceutical composition according to  claim 2  which is a suspension. 
     
     
       16. Pharmaceutical composition comprising calcipotriol monohydrate according to  claim 12  and a pharmaceutically acceptable vehicle, with a content of the calcipotriol monohydrate being  1 - 100  μg/g of the composition. 
     
     
       17. Pharmaceutical composition comprising calcipotriol monohydrate according to  claim 13  and a pharmaceutically acceptable vehicle, with a content of the calcipotriol monohydrate being  1 - 100  μg/g of the composition. 
     
     
       18. Pharmaceutical composition comprising calcipotriol monohydrate according to  claim 14  and a pharmaceutically acceptable vehicle, with a content of the calcipotriol monohydrate being  1 - 100  μg/g of the composition. 
     
     
       19. Pharmaceutical composition comprising calcipotriol monohydrate according to  claim 15  and a pharmaceutically acceptable vehicle, with a content of the calcipotriol monohydrate being  1 - 100  μg/g of the composition.